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Nasopharyngeal Cancer

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Links to Articles

* Nasopharyngeal Cancer by National Cancer Institute

* Nasopharyngeal Cancer Types by Cancer Research UK

* Nasopharyngeal Cancer or Sinus Infection by sinusinfectionhelp.com

* A Genetic Epidemiological Study of
Nasopharyngeal Carcinoma by Bingjian Feng

* Traditional Cantonese diet and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China by Wei-Hua Jia, et al.

* Video: 認識鼻咽癌

* 鼻咽癌病友手冊---如何戰勝鼻咽癌 by 黃 淑 珍

* 鼻咽癌治療 by 奇美醫院電腦刀中心主網站

* 長期耳鳴 原來罹鼻咽癌 by 管瑞平

* Familial Tendency and Risk of Nasopharyngeal Carcinoma in Taiwan: Effects of Covariates on Risk by Wan-Lun Hsu, et al.

* Cancer Patterns in Nasopharyngeal Carcinoma Multiplex Families in Taiwan by
Kelly J. Yu, et al.

* Symptom Distress, Catastrophic Thinking, and Hope in Nasopharyngeal Carcinoma Patients by Lai YH, et al.

 

• Celiac Disease
• Nasopharyngeal Carcinoma
• Lactose Intolerance
• Esophageal Cancer
• Stevens-Johnson Syndrome
• Ankylosing Spondylitis

Nasopharyngeal Cancer: Multidisciplinary Management by Jiade J. Lu, et al.

 

The Official Patient's Sourcebook on Nasopharyngeal Cancer: A Revised and Updated Directory for the Internet Age

 

 

The Epstein–Barr virus (EBV) is a virus of the herpes family, which includes herpes simplex virus 1 and 2, and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis. It is also associated with particular forms of cancer, particularly Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma, and central nervous system lymphomas associated with HIV. Finally, there is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis.

Most people become infected with EBV and gain adaptive immunity.

 

 

Excerpts from Wikipedia.org

Nasopharyngeal carcinoma (NPC; 鼻咽癌) is the most common cancer originating in the nasopharynx, the uppermost region of the pharynx or "throat", where the nasal passages and auditory tubes join the remainder of the upper respiratory tract. NPC differs significantly from other cancers of the head and neck in its occurrence, causes, clinical behavior, and treatment. It is vastly more common in certain regions of East Asia and Africa than elsewhere, with viral, dietary and genetic factors implicated in its causation. It is most common in males.

Epidemiology: NPC is uncommon in the United States and most other nations, but is extremely common in southern regions of China, particularly in Guangdong accounting for 18% of all cancers in China. It is sometimes referred to as Cantonese cancer because it occurs in about 25 cases per 100,000 people in this region, 25 times higher than the rest of the world. It is also quite common in Taiwan. This could be due to the South East Asian diet which typically includes consumption of salted vegetables, fish and meat. While NPC is seen primarily in middle-aged persons in Asia, a high proportion of African cases appear in children. The cause of increased risk for NPC in these endemic regions is not entirely clear.

Symptoms and signs: Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy may occur with widespread disease.

Causes: EBV (Epstein-Barr virus) NPC is the most common epithelial cancer in adults. The detection of nuclear antigen associated with Epstein-Barr virus (EBNA) and viral DNA in NPC type 2 and 3, has revealed that EBV can infect epithelial cells and is associated with their transformation . The etiology of NPC (particularly the endemic form) seems to follow a multi-step process, in which EBV, ethnic background, and environmental carcinogens all seem to play an important role. Lo et al. showed that EBV DNA was detectable in the plasma samples of 96% of patients with non-keratinizing NPC, compared with only 7% in controls. More importantly, EBV DNA levels appear to correlate with treatment response and they may predict disease recurrence, suggesting that they may be an independent indicator of prognosis. In adults, other likely etiological factors include genetic susceptibility, consumption of food (in particular salted fish) containing carcinogenic volatile nitrosamines, and as in children, EBV .

Prognosis: Prognostic factors Stage at presentation is the most prognostic factor. The 5-year disease-specific survival (DSS) is as follow: • For stage I à 98% • For stage II A-B à 95% • For stage III à 86% • For stage IV A-B à 73%

 

 

 

Geographic Distribution of Nasopharyngeal Carcinoma

 

* The Enigmatic Epidemiology of Nasopharyngeal Carcinoma by Ellen T. Chang, et al.

Age-standardized (world) Incidence Rates of Nasopharyngeal Cancer in Selected Populations

Excerpts: In most regions, the age-standardized incidence rate of NPC for both males and females is <1 per 100,000 person-years. However, dramatically elevated rates are observed in the Cantonese population of southern China (including Hong Kong), and intermediate rates are observed in several indigenous populations in Southeast Asia, and in natives of the Arctic region, North Africa, and the Middle East. Even within China, there is at least 50-fold variation in NPC incidence across regions, with rates generally increasing from northern China (e.g., Beijing and Tianjin) to southern China (e.g., Hong Kong). ...

Although geographic regions have generally been classified as high- or low-incidence areas, the racial/ethnic distribution of NPC within regions is far from uniform. In the southeastern Chinese province of Guangdong, where the overall NPC incidence rate is >20 per 100,000 person-years among males, rates in Cantonese speakers are double those in other dialect groups such as the Hakka, Hokkien, and Chiu Chau. Likewise, in the Malaysian state of Selangor, rates in Chinese residents have historically been highest among Cantonese, intermediate among Khek (Hakka), and lowest among Hokkien and Teochiu. In the United States, rates are highest among Chinese Americans, followed distantly by Filipino Americans, then Japanese Americans, Blacks, Hispanics, and finally Whites.

In Southeast Asia, NPC risk seems to vary with degree of racial and social admixture with southern Chinese. Incidence is low among Singapore Indians who have had practically no intermingling with Chinese, but much higher in the Thai, Macaonese, and Malay indigenous populations, which have a history of intermarriage with Chinese ancestors. Similarly, rates in Ho Chi Minh City are roughly half those in Hanoi, where a higher proportion of the population is of ethnic Chinese descent. Close ties have existed between Japan and China for thousands of years, but mainly with northern China, and the incidence of NPC in Japan is low....

 

 

* Nasopharyngeal Carcinoma as a Paradigm of Cancer Genetics by Malcolm J. Simons

Abstract: The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20-21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modern day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome combinations, or haplotypes (e.g. HLA-A2-B46), whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently, a strength of association reflecting the 30-50-fold difference in incidence between highest risk Cantonese and lowest-risk Indians. The prototypic haplotype HLA-A2-B46 extends over megabases. An upstream DNA segment (near HLA-DPA1), has close similarity to Gorilla, with no obvious homology to Chimpanzee in current databases, suggesting that a reticulate model of primate evolution may be more appropriate than simple phylogeny. The DNA variation level in this segment is high enough for it to be a hominin remnant. HLA-B46 arose in mongoloids and remains largely limited to Chinese so the question arises as to whether the hominin candidate segment indicates an eastward trek of Homo neanderthalensis or the survival of much earlier Homo erectus? In 2011 sequencing technologies have finally caught up with the requirement to separate parental haplotypes. Recently achieved chromosome separation for whole genome di-haploid genetic and epigenetic analysis of parental inheritance in single individuals will reveal interacting patterns of multi-locus haplotypes as humans move in and through successive environments, thus providing definitive information on the genetic affinities between extant populations, and of the migrations that have led to the global distribution of modern Homo. The challenge can now be met of seeking HLA-associated locations both within and outside the HLA complex on each of the pair of chromosomes. More broadly, for every disease, genetic risk detection will require resolution of the diploid genome as a di-haplome. In the context of NPC, HLA genetic risk complete autosomal di-haplomic sequencing will enable testing of the Wee unitary origin hypothesis of NPC risk even among populations with no apparent mongoloid affinity.

 

* Nasopharyngeal Carcinoma in the Northeastern States of India by Kataki AC, et al.

Abstract: Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as about 20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100 000, which is among the highest recorded rates. By contrast, in Assam, one of the so-called Hill States but not itself a hilly state, NPC is much less common. The Northeastern region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.

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Inuit

The Inuit are a group of culturally similar indigenous peoples inhabiting the Arctic regions of Canada (Northwest Territories, Nunatsiavut, Nunavik, Nunavut, Nunatukavut), Denmark (Greenland), Russia (Siberia) and the United States (Alaska). Inuit means “the people” in the Inuktitut language. An Inuk is an Inuit person. The Inuit language is grouped under Eskimo-Aleut languages.

Eskimo–Aleut does not have any genetic relationship to any of the world's other language families that is generally accepted by linguists at the present time. There is general agreement that it is not closely related to the other language families of North America. The more credible proposals on the external relations of Eskimo–Aleut all concern one or more of the language families of northern Eurasia. One of the first such proposals was made by the pioneering Danish linguist Rasmus Rask in 1818, upon noticing similarities between Greenlandic Eskimo and Finnish. Perhaps the most fully developed such proposal to date is Michael Fortescue's Uralo-Siberian hypothesis, published in 1998. More recently Joseph Greenberg (2000–2002) has suggested grouping Eskimo–Aleut with all of the language families of northern Eurasia, with the exception of Yeniseian, in a proposed language family called Eurasiatic. Such proposals remain controversial.

Inuit are the descendants of what anthropologists call the Thule culture, who emerged from western Alaska around 1000 AD and spread eastwards across the Arctic. They displaced the related Dorset culture, the last major Paleo-Eskimo culture (in Inuktitut, called the Tuniit).

The Inuit have traditionally been hunters and fishers. They still hunt whales (esp. bowhead whale), walrus, caribou, seal, polar bears, muskoxen, birds, and at times other less commonly eaten animals such as the Arctic Fox. The typical Inuit diet is high in protein and very high in fat – in their traditional diets, Inuit consumed an average of 75% of their daily energy intake from fat. While it is not possible to cultivate plants for food in the Arctic, the Inuit have traditionally gathered those that are naturally available. Grasses, tubers, roots, stems, berries, and seaweed (kuanniq or edible seaweed) were collected and preserved depending on the season and the location. There is a vast array of different hunting technologies that the Inuit used to gather their food.

In the 1920s anthropologist Vilhjalmur Stefansson lived with and studied a group of Inuit. The study focused on the fact that the Inuit's extremely low-carbohydrate diet had no adverse effects on their health, nor indeed, Stefansson's own health. Stefansson (1946) also observed that the Inuit were able to get the necessary vitamins they needed from their traditional winter diet, which did not contain any plant matter. In particular, he found that adequate vitamin C could be obtained from items in their traditional diet of raw meat such as Ringed Seal liver and whale skin (muktuk). While there was considerable scepticism when he reported these findings, they have been borne out in recent studies.

 

* Nasopharyngeal Cancer in Greenland. The incidence in an Arctic Eskimo population by Nielsen NH, et al.

Abstract: Nasopharyngeal cancer is very common among the Chinese in various parts of the world, particularly Southern China, and frequent in certain other Mongoloid groups in Southeast Asia. Also, the incidence among the Eskimos of the western Canadian Arctic and Alaska is considerably higher than would be expected. Ths paper reports for the first time the incidence of nasopharyngeal cancer among native Greenlanders, an Eskimo population with some admixture of Caucasian blood. During 1955-1976, thirty-five cases of nasopharyngeal cancer were diagnosed. Ninety-four per cent (33 cases) were squamous cell carcinomas, including lymphoepitheliomas. Incidence rates 1965-1976, age adjusted to the "world" population distribution, were 12.3 and 8.5 per 100,000 per annum for males and females respectively. These rates are among the highest recorded in the world and significantly higher than among the Caucasian population in Denmark. Compared with other high risk populations nasopharyngeal cancer among Greenlanders had an older age distribution and a lower male-to-female sex ratio. An additional 11 cases with malignant involvement, seeminly confined only to cervical lymph nodes, may have included some undiagnosed nasopharyngeal cancers. Thus the calculated incidence rates of this study could represent only minimum rates. Further research is needed especially with regard to the HL-A profile and to possible traces of Epstein-Barr virus infection.

 

* Cancer Susceptibility in Nasopharyngeal Carcinoma Families—A Population-Based Cohort Study by Jeppe Friborg, et al.

Abstract: Undifferentiated nasopharyngeal carcinoma is a result of environmental factors, in particular EBV infection, affecting genetically susceptible individuals. The familial risk of nasopharyngeal carcinoma is among the highest of any malignancy. Whether this susceptibility is restricted to nasopharyngeal carcinoma is unknown as information on the risk of other cancers in relatives is limited. We did a population-based study of the cancer incidence in nasopharyngeal carcinoma families in Greenland, a nasopharyngeal carcinoma–endemic area. Using population-based registers, a cohort of all persons born in Greenland was followed from 1973 to 2002. In this cohort, 134 individuals developed nasopharyngeal carcinoma and their relatives were identified through registers and interviews. Subsequently, the occurrence of cancer was determined by linkage to the population-based cancer register and the risk of cancer in nasopharyngeal carcinoma relatives and nonrelatives compared by relative risks. Among 766 first-degree relatives, the relative risk of nasopharyngeal carcinoma following the family index case was 8.0 [95% confidence interval (95% CI), 4.1-14.0]. Sex and age of the relative or the index case had no modifying effect on the familial risk of nasopharyngeal carcinoma. The relative risks of carcinoma of the salivary glands, 8.4 (95% CI, 2.7-19.5), and uterine cervix, 2.2 (95% CI, 1.1-3.9), were also significantly increased. In families with multiple cases of nasopharyngeal carcinoma, the risk of other cancers than nasopharyngeal carcinoma was further increased. These results indicate that the increased risk of cancer in nasopharyngeal carcinoma families is not restricted to nasopharyngeal carcinoma, but extends to the virally associated cancers of the salivary glands and cervical uteri.

 

* Epidemiology of Nasopharyngeal and Salivary Gland Carcinoma in Greenland by Albeck H, et al.

Abstract: From 1950 to 1989 one hundred and forty-four cases of either undifferentiated nasopharyngeal carcinoma (NPC) or salivary gland carcinoma (SGC) were diagnosed in Greenlanders, all born in Greenland. The Greenland SGC is an anaplastic carcinoma with histopathology and electronmicroscopic cytopathological alterations as found in undifferentiated NPC. Both NPC and SGC from Greenland and Alaska are associated with Epstein-Barr virus infection. The incidence rate of NPC based on newly diagnosed cases during the last 15 years is 12.7 for men and 9.2 for women. The same figures for anaplastic SGC are 3.4 and 3.1. These are among the highest incidence rates of Epstein-Barr virus associated carcinomas on record. From 1950 to 1989 there has been an increase in the rate of NPC. From the cumulated rate, it can be predicted that the number of cases will continue to increase during the years to come. During the ten year period 1980 to 1989 patients were questioned about their childhood life style and the family history was taken. The Inuit lifestyle is quite different from that of Europeans and Chinese, but in common with Chinese from Guangzhou (formerly Canton) Greenlanders have a high consumption of fish, fresh as well as dried. Familial clustering has been rarely reported, but in the present investigation 27% of the patients diagnosed between 1980 and 1990 had a positive familial history with one or more confirmed cases among first degree relatives

 

* Genetic Epidemiology of Greenland by Bent Harvald

Abstract: The Inuit (Eskimo) gene pool is in many respects similar to that of East Asian populations. Some polymorphisms imply frequent occurrence of disorders comparatively rare in Western Europe (e.g. lactose and sucrose malabsorptions). Low frequencies of alleles for slow isoniazid acetylation and sparteine/debrisoquine oxidation indicate slow elimination of a multitude of drugs. Autoimmune disorders (e.g. rheumatoid arthritis, insulin-dependent diabetes mellitus, Graves' disease and psoriasis) are rare, possibly explained by the associations of these disorders with HLA-alleles rare in the Inuit (e.g. HLA-B8). A correspondingly high incidence of reactive arthritis may be explained by a frequent HLA-B27 allele. The prevalence of disorders due to instability of mesenchymal tissues (e.g. spondylolisthesis, osteoarthrosis, hernia, heart block) still requires a biochemical explanation. Attention is drawn to the urgency of genetic studies in the Arctic because of the accelerating hybridization of the Inuit in all circumpolar areas.

 

* Heterogeneity of Taiwan's Indigenous Population: Possible relation to prehistoric Mongoloid dispersals by M. Lin, et al.

Abstract: Taiwan's 9 indigenous tribes (Tsou, Bunun, Rukai, Atayal, Saisiat, Ami, Puyuma, Yami, Paiwan) are highly homogeneous within each tribe, but diversified among the different tribes due to long-term isolation, most probably since Taiwan became an island about 12,000 years ago. Homogeneity of each tribe is evidenced by many HLA-A,B,C alleles having the world's highest ever reported frequencies, e.g. A24 (86.3%), A26 (18.8%), Cw10 (36.8%), Cw7 (66%), Cw8 (32.1%), B13 (27.9%), B62 (37.4%), B75 (18%), B39 (53.5%), B60 (33.3%), and B48 (24%). Also, all of these tribes have HLA class I haplotype frequencies greater than 10%, with A24-Cw7-B39 in Saisiat (44.5%) being the highest, suggesting Taiwan's indigenous tribes are probably the most homogeneous ( the "purest") population in the world. A24-Cw8-B48, A24-Cw10-B60 and A24-Cw9-B61 found common to many Taiwan indigenous tribes, have also been observed in Maori, Papua New Guinea Highlanders, Orochons, Mongolians, Inuit, Japanese, Man, Buryat, Yakut, Tlingit, Tibetans and Thais. These findings suggest Taiwan's indigenous groups are more or less genetically related to both northern and southern Asians. Principal component analysis and the phylogenetic tree (using the neighbor-joining method) showed close relationship between the indigenous groups and Oceanians. This relationship supports the hypothesis that Taiwan was probably on the route of prehistoric Mongoloid dispersals that most likely took place along the coastal lowland of the Asian continent (which is under the sea today). Cultural anthropology also suggests a relationship between Taiwan's indigenous tribes and southern Asians and to a lesser extent, northern Asians. However, the indigenous groups show little genetic relationship to current southern and northern Han Chinese.

 

Map: 史前人類遷移的途徑 from 從DNA 的研究看台灣原住民的來源 by 林媽利

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Baiyue

Qin empire and Yue peoples, 210 BC: Dong-Yue, Nan-Yue

The Baiyue (百越), Hundred Yue or Yue (越) is a loose term denoting various partly sinicized or un-sinicized peoples who inhabited southern China and northern Vietnam between the first millennium BC and the first millennium AD. In the warring states period, the word "Yue" referred to the State of Yue in Zhejiang. The later kingdoms of Minyue in Fujian and Nanyue in Guangdong are both considered Baiyue states. Chinese writers depicted the Yue as barbarians who had tattoos, lived in primitive conditions, and lacked such technology as bows, arrows, horses and chariots. The Baiyue have been compared to the lost tribes of Israel, with a great deal of speculation among Chinese historians concerning who they were and what happened to them. Many of the ethnic groups now inhabiting southern China and northern Vietnam are thought to be descendants of the Baiyue or have some connection to the ancient Baiyue. Variations of the name continue to be used by both the Cantonese (粤) and by the Vietnamese (越) to refer to themselves.

Historian Luo Xianglin has suggested that these peoples shared a common ancestry with the Xia Dynasty. There is little evidence, however, that the Yue peoples held any common identity.

Map of Xia Dynasty

Most Yue peoples were eventually sinicized, and continue to live in Zhejiang and Guangdong, the Kam-Tai (Daic): Zhuang, Buyi, Dai, Sui (Shui), Kam (Dong), Hlai (Li), Mulam, Maonan, Ong-Be (Lingao), Thai, Lao, Shan, and Vietnamese people retained their ethnic identities. Some of these peoples migrated to Mon-Khmer areas after ruled by officials of Han Chinese emperors.

 

* Is Nasopharyngeal Cancer Really a "Cantonese Cancer"? by JT Wee, et al.

Abstract: Nasopharyngeal cancer (NPC) is endemic in Southern China, with Guandong province and Hong Kong reporting some of the highest incidences in the world. The journal Science has called it a "Cantonese cancer". We propose that in fact NPC is a cancer that originated in the Bai Yue ("proto Tai Kadai" or "proto Austronesian" or "proto Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage. However, the work by John Ho raised the profile of NPC, and because of the high incidence of NPC in Hong Kong and Guangzhou, NPC became known as a Cantonese cancer. We searched historical articles, articles cited in PubMed, Google, monographs, books and Internet articles relating to genetics of the peoples with high populations of NPC. The migration history of these various peoples was extensively researched, and where possible, their genetic fingerprint identified to corroborate with historical accounts. Genetic and anthropological evidence suggest there are a lot of similarities between the Bai Yue and the aboriginal peoples of Borneo and Northeast India; between Inuit of Greenland, Austronesian Mayalo Polynesians of Southeast Asia and Polynesians of Oceania, suggesting some common ancestry. Genetic studies also suggest the present Cantonese, Minnans and Hakkas are probably an admixture of northern Han and southern Bai Yue. All these populations have a high incidence of NPC. Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

Excerpt: Before the last ice age, continental Asia extended to Japan and Taiwan through two coastal landmasses known as Tunghailand and Nanhailand (from the Gulf of Tonkin to Japan) and to Borneo and Java through Sundaland (now the Gulf of Siam and Java Sea); now all are under the sea after the rise in sea levels (Figure 3). The original southern China aborigines (protoBaiyue) probably wandered freely along this coastal region, but after the ice age and the following rising sea levels, they became isolated on the islands of Taiwan, Hainan, Borneo, and islandic Southeast Asia. Some of these people were also believed to have migrated north and across the Bering Strait into Alaska, Greenland, and the Americas.

Origins of the Polynesians

 

* The Origin of Minnan & Hakka, the So-Called "Taiwanese" Inferred by HLA Study by M. Lin

Abstract: The Minnan and Hakka people groups, the so-called "Taiwanese", are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai-Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggest that this haplotype is the most well conserved ancient haplotype of the Yueh (從組織抗原推論閩南人及客家人，所謂「台灣人」的來源 by 林媽利).

(Minnan, Hakka, Thai Chinese, Singapore Chinese, Thais, Vietnamese, Buyi, Southern Han, Miao)

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Sarawak, Borneo

The Dayak or Dyak are the peoples indigenous to Borneo. It is a loose term for over 200 riverine and hill-dwelling ethnic subgroups, located principally in the interior of Borneo, each with its own dialect, customs, laws, territory and culture, although common distinguishing traits are readily identifiable. Dayaks are categorised as part of wider Austronesian-speaking populations in Asia. The Dayak were animist in belief; however many converted to Christianity, and some to Islam more recently. Estimates for the Dayak population range from 2 to 4 million.

Common interpretations in modern anthropology agree that nearly all indigenous peoples of South East Asia, including the Dayaks, are descendants of a larger more common Austronesian migration from Asia, regarded to have settled in the South East Asian Archipelago some 3,000 years ago. The first populations spoke various languages and dialects now termed under the collective Austronesian Lingua, from which Dayak languages are traced. About 2,450 years ago, metallurgy was introduced and subsequently became widespread.

The main ethnic groups of Dayaks are the Bakumpai and Dayak Bukit of South Kalimantan, The Ngajus, Baritos, Benuaqs of East Kalimantan, the Kayan and Kenyah groups and their subtribes in Central Borneo and the Ibans, Embaloh (Maloh), Kayan, Kenyah, Penan, Kelabit, Lun Bawang and Taman populations in the Kapuas and Sarawak regions. Other populations include the Ahe, Jagoi, Selakau, Bidayuh, and Kutais.

 

Bidayuh

(Photo From terencelau.com)

 

Iban

(Iban girls dressed in full Iban (women) attire during Gawai festivals)

 

* High Incidence of Nasopharyngeal Carcinoma in Native People of Sarawak, Borneo Island by Beena C. R. Devi, et al.

Abstract: Nasopharyngeal cancer (NPC) is generally a rare malignancy with a few well-known exceptions, notably South-East China. In this article, we describe evidence of a high risk of NPC in the population of Sarawak State, Malaysia, and particularly in one native ethnic group. Sarawak State is one of the two provinces of Malaysia located on the island of Borneo. The native population (71.6%) includes the Iban, Malay, Bidayuh, Melanau, and diverse smaller ethnic groups. The Chinese are the largest nonindigenous group (27.5%). We identified 392 newly diagnosed cases (292 males and 100 females) of NPC in 1996–1998 in Malaysian citizens, permanent residents of Sarawak. Age-standardized rates by sex and ethnic group were compared with the highest rates in the world. The age-adjusted rate (ASR) in Sarawak residents was 13.5/100,000 [95% confidence interval (CI) 12.2–15.0] and 6.2/100,000 (95% CI 5.7–6.7) in males and females, respectively. The risk in the Bidayuh people was 2.3-fold (M) and 1.9-fold (F) higher than the Sarawak average, and about 50% higher than that in Hong Kong—the highest recorded by any population-based registry for the same period. Local dietary habits, environmental exposures, and genetic susceptibility deserve investigation in this population.

Age-standardized rates (100,000) of NPC in Sarawak and in the 10 populations in Cancer Incidence in Five Continents

Excerpt: We were able to assess the magnitude of the phenomenon and provide comparative age-standardized figures showing that native Sarawak people exhibit the highest rates in the world. Incidence is moderately high in several other countries in South-East Asia such as Thailand and Viet Nam where Chinese immigrants have mixed with the local population for centuries. Studies of migrants from high-risk Asian countries to the United States show that such individuals retain a relatively high risk, compared with the US population as do North African migrants to Israel. The high risk in native people of Sarawak, however, is unlikely to be the result of blending with citizens of Chinese descent that in this country, as in Singapore, are a distinct ethnic group.

Established causes of NPC are the ubiquitous EBV, tobacco smoking, and consumption of Chinese-style salted fish, particularly in childhood. Salted fish has been shown to increase the risk of the disease in Malaysian Chinese while no studies linking NPC to specific dietary habits of native people have been published. In the high-risk Hong Kong population, incidence rates have declined by 30% from 1980 to 1995, proving that environmental factors are a relevant component of the aetiology of the disease. Nevertheless, because of the peculiar geographical distribution of the disease, which does not match the prevalence of the factors described, none of these alone is likely to be sufficient to cause the disease. Interaction between environmental causes and genetic predisposition would be consistent with the wide range of risk in the world and variable association with established risk factors, as well as with the pattern of risk observed in migrant populations. Some haplotypes of the HLA system have been associated with increased risk of NPC in several high-risk populations including Malay but susceptibility genes have not been identified as yet. A specific Km allele that was associated with NPC cases from Northern Africa was not more common in NPC Malaysian Chinese or Malay patients compared to controls. The people of Sarawak might be an example of genetic drift suitable for studies of genetic linkage. Traditional dietary habits and immune response to EBV also deserve further investigation.

 

* HLA Polymorphism in Malay Sub-ethnic Groups in Penninsular Malaysia by Edinur Hisham Atan

Map Showing the Geographic Location of East and West Malaysia Within South East Asia, International and State Boundaries, Where the Samples Were Collected and the Malays Migration Pattern

 

* Ancient Jades Map 3,000 Years of Prehistoric Exchange in Southeast Asia by Hsiao-Chun Hung, et al.

The distribution of Taiwan nephrite artifacts in Southeast Asia (from Ancient Jades Map 3,000 Years of Prehistoric Exchange in Southeast Asia by Hsiao-Chun Hung, et al.) . The green zone represents the currently known distribution of Taiwan nephrite artifacts. The green triangle locates the Fengtian nephrite deposit. Yellow stars represent sites outside Taiwan with positively identified Fengtian nephrite artifacts (Taiwan itself has >108 jade-bearing sites, and these cannot be shown individually). Blue stars represent sites with jade artifacts of possible Fengtian origin. Black circles represent sites that have identified nephrite of non-Fengtian origin.

 

* Y-chromosomal STRs Haplotypes in the Taiwanese Paiwan Population by Fang-Chin Wu, et al.

MDS Plot Based on Pairwise Φst Values Calculated for the Paiwan (filled circle) and Ten Reference Populations (open circles)

(Bidayuh, Minnan (China), Taiwan (Taiwanese), Melanau, Iban)

 

* Haplotype Diversity of 17 Y-Chromosomal STRs in Three Native Sarawak Populations (Iban, Bidayuh and Melanau) in East Malaysia by YM Chang YM

Abstract: 17 Y-STRs (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4, DYS437, DYS438 and DYS448) have been analyzed in 320 male individuals from Sarawak, an eastern state of Malaysia on the Borneo island using the AmpFlSTR Y-filer (Applied Biosystems, Foster City, CA). These individuals were from three indigenous ethnic groups in Sarawak comprising of 103 Ibans, 113 Bidayuhs and 104 Melanaus. The observed 17-loci haplotypes and the individual allele frequencies for each locus were estimated, whilst the locus diversity, haplotype diversity and discrimination capacity were calculated in the three groups. Analysis of molecular variance (AMOVA) indicated that 87.6% of the haplotypic variation was found within population and 12.4% between populations (fixation index F(ST)=0.124, p=0.000). This study has revealed that the indigenous populations in Sarawak are distinctly different to each other, and to the three major ethnic groups in Malaysia (Malays, Chinese and Indians), with the Melanaus having a strikingly high degree of shared haplotypes within. There are rare unusual variants and microvariants that were not present in Malaysian Malay, Chinese or Indian groups. In addition, occurrences of DYS385 duplications which were only noticeably present in Chinese group previously was also observed in the Iban group whilst null alleles were detected at several Y-loci (namely DYS19, DYS392, DYS389II and DYS448) in the Iban and Melanau groups.

* Ancestry of the Iban Is Predominantly Southeast Asian: Genetic Evidence from Autosomal, Mitochondrial, and Y Chromosomes by Tatum S. Simonson, et al.

Abstract: Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data

Excerpt: Uniparental marker analyses also indicate a strong genetic influence from mainland Southeast Asia, although there is substantial influence from paternal lineages appears to be associated with northern Asian groups (Table S2; Table S3). The NYR haplogroup frequencies in the Iban and their relation to other populations are shown in Fig. 3. PC1 separates the Taiwanese Aborigines, Philippines, Nusa Tenggara, and Moluccas from the Iban, other Southeast Asian populations, and the Chinese populations. The separation between the Iban and an aboriginal Taiwanese group based on PC1 argues against strong Taiwanese influence on the Iban. On PC2, the Iban, Vietnamese, Chinese, Philippines, and Aboriginal Taiwanese cluster separately from the Malaysian, Southern Bornean, and to the greatest extreme, the Nusa Tenggara and Moluccas populations.

Among the 89 Iban males, the NRY O sub-haplogroups (frequency of O2a = 0.42 and O3 = 0.40) are the most frequent. Haplogroup O2a is found at high frequency throughout Southeast Asia and is common among indigenous, isolated populations such as the Hainan Aborigines located off the mainland coast of Southeast Asia. These results suggest a similar prehistory in the Iban and these Southeast Asian populations. The next most frequent NRY haplogroup is O3, which is distributed throughout East Asia, ISEA, and Oceania, and may represent a substantial contribution from Taiwan. Haplogroups O1, K, C, and F are also present, but at lower frequencies (0.04, 0.08, 0.04, and 0.01, respectively). Haplogroup O1 may reflect the impact of the Out-of-Taiwan migration, although better resolution is necessary to specify Taiwan as the source population. The K, C, and F haplogroups are thought to have originated in Melanesian, Asian, and out-of-Africa migrant populations, respectively. The NRY haplogroup frequencies reflect male-specific gene flow from Southeast Asia, although they do not preclude more recent but less substantial contributions from northern populations such as that of Taiwan.

 

* Genomic Analysis of Mitochondrial DNA in the Indigenous Groups of Malaysia by Lih-Chun Hong, et al.

Abstract: Polymorphisms in the control and coding regions of mitochondrial DNA (mtDNA) were analyzed in four Indigenous groups (N=188). A total of 64 different mtDNA haplotypes were elucidated. Of the 64 sequences observed, 44% were unique and 56% were shared by more than one individual. We report seven novel polymorphisms, with three in the HVS-1 and four in HVS-2 segments that have hitherto not been reported. These polymorphisms have been submitted to MITOMAP database. Most mtDNA variants belonged to three major haplogroups M, N and R. The majority of the haplogroups were found to be exclusive to the Indigenous groups in Malaysia. The most frequent were haplogroups including M21a and R21, which both reflect very old lineages, deeply rooted in South East Asian populations. This was evident in about 80% of the Negritos (Jehai and Kensiu) that were genotyped. Haplogroups N21 (24%) and N22 (8%) were predominantly found in Temuan whilst haplogroup N9a6a was predominant in Bidayuh (40%). Haplogroups indicative of South and Central Asia distributions were observed in variable frequencies. The Temuan comprise the most diverse group followed by Jehai and Bidayuh. The least diverse were the Kensiu. In our study cohort, the lower levels of genetic diversity in these four groups in contrast to majority of the Asian population (0.798 - 0.872) are indicative of genetic drift and may reflect bottleneck effects due to relatively long periods of isolation. The 9bp deletion in the MT-CO2/MT-TK (tRNALys) intergenic region of mtDNA (n.p. 8271-8281) was detected in 10.1% of the participants investigated. This deletion was identified in a Kensiu individual, five Bidayuh and the majority of Temuan (28%), but not detected in Jehai. Our results support the current view that Malaysia is home to some of the oldest groups to have migrated out of Africa.

_________________________________________________________________

 

Taiwan

 

* Ancient Migration Routes of Austronesian-Speaking Populations in Oceanic Southeast Asia and Melanesia Might Mimic the Spread of Nasopharyngeal Carcinoma by J Trejaut, et al.

Abstract: Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the "Out of Africa" hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS I & II) among 1400 individuals from island Southeast Asia (ISEA), Taiwan and Fujian and supplemented with the analysis of relevant coding region polymorphisms. Lineages that best represented a clade (a branch of the genetic tree) in the phylogeny were further analyzed using complete genomic mtDNA sequencing. Finally, these complete mtDNA sequences were used to construct a most parsimonious tree which now constitutes the most up-to-date mtDNA dataset available on ISEA and Taiwan. This analysis has exposed new insights of the evolutionary history of insular Asia and has strong implications in assessing possible correlations with linguistic, archaeology, demography and the NPC distribution in populations within these regions. To obtain a more objective and balanced genetic point of view, slowly evolving biallelic Y single nucleotide polymorphism (Y-SNP) was also analyzed. As in the first step above, the technique was first applied to determine affinities (macro analysis) between populations of insular Asia. Secondly, sixteen Y short tandem repeats (Y-STR) were used as they allow deeper insight (micro analysis) into the relationship between individuals of a same region. Together, mtDNA and NRY allowed a better definition of the relational, demographic, cultural and genetic components that constitute the make up of the present day peoples of ISEA. Outstanding findings were obtained on the routes of migration that occurred along with the spread of NPC during the settlement of insular Asia. The results of this analysis will be discussed using a conceptual approach.

 

* Cancer Mortality Analysis Among Aborigines in Taiwan by YC Ko, et al.

Abstract: Mortality among Aborigines tribes in Taiwan from malignant neoplasms in the 1971-80 and 1981-90 decades were analyzed. Sex and tribe specific standardized mortality ratios were calculated from death certificate data and compared with the number of expected deaths derived from the cancer mortality of the entire population of Taiwan. Mortality due to oral cancer was statistically significantly higher than expected among Paiwan men in the 1971-80 decade and among Paiwan women from 1971-80 and 1981-90; as was mortality from nasopharyngeal cancer among Bunun, Paiwan and Rukai men from 1981-90 and among Bunun and Paiwan women from 1971-80 and 1981-90; mortality due to stomach cancer among the Atayal, Bunun and Paiwan people from 1971-80 and 1981-90, among Rukai men from 1971-80 and among the Tsou and mixed group women from 1981-90; mortality from liver cancer among Atayal and Bunun men in 1971-80, among Bunun women from 1971-80 and 1981-90 and among Paiwan women in 1981-90; mortality due to nasal cavity, middle ear and paranasal sinuses cancer among Rukai men from 1981-90; and mortality due to bone cancer among Tsou men and Atayal women from 1981-90. Mortality due to colorectal cancer was statistically significantly lower than expected among mixed group men from 1971-80 and in Atayal women from 1981-90; as was mortality from lung cancer among Atayal men and Paiwan women from 1971-80 and among Paiwan and mixed group men in the 1981-90 decade. Overall, the standardized mortality ratio of all cancers in aborigines was a little higher than in the general population of Taiwan. However, differences for ratio or site existed in different tribes.

 

Bunun

 

Paiwan

 

Rukai

 

* Genetic Susceptibility to Nasopharyngeal Carcinoma Within the HLA-A Locus in Taiwanese by Cheng-Chan Lu, et al.

Abstract: NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR
2.50, pc
0.020 (study population); OR
3.73, pc
0.0030 (>40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2B46individuals are at greater risk for NPC than A2–B46– individuals in both the population studied and the >40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2B38 individuals were at higher risk than A2–B38– individuals in both the population studied and the >40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR
3.97, pc
0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus.

 

HLA-B38

HLA-B38 is a split antigen of the broad antigen B16, and is a sister type of B39. The B*3801 allele is more common in Eastern, Southern and Southeastern Europe, while the B*3802 allele is more common in the Far East.

 

HLA B*3801 Frequencies

Population	(%)
Israel Ashk. and Non Ashk. Jews	6.9
Croatia	6.7
Italy North	6.7
Azores Central Islands	5.4
Czech Republic	4.7
Georgia Tibilisi Georgians	4.6
Macedonia (4)	4.6
Spain Eastern Andalusia	4.1
Georgia Svaneti Svans	3.8
Bulgaria	3.6
Romanian	3.2
Tunisia	3.0
Thailand	2.8
Israel Arab Druse	2.5
Tunisia Tunis	2.3
Indig. Australian Cape York Penin.	2.0
France South East	1.9
Georgia Tibilisi Kurds	1.7
Australia New South Wales	1.5
China Guangzhou	1.5
China Yunnan Lisu	1.4
Jordan Amman	1.4
Morocco Nador Metalsa Class I	1.4
China South Han	1.2
Saudi Arabia Guraiat and Hail	1.2
Finland	1.1
American Samoa	1.0
China North Han	1.0
India North Hindus	1.0
Hong Kong Chinese	0.9
Ireland Northern	0.9
China Beijing	0.8
Ireland South	0.8

HLA B*3802 Frequencies

Population	(%)
Taiwan Tao	11.0
China Guangxi Maonan	8.3
China South Han	7.1
Singapore Javan. Indonesians	7.1
Singapore Chinese Han	6.4
Taiwan Minnan pop 1	6.4
China Guangzhou	6.0
Philippines Ivatan	6.0
Hong Kong Chinese	5.4
Singapore Chinese	4.7
Singapore Riau Malay	4.5
China Guangzhou Han	4.3
India West Bhils	4.0
Taiwan Hakka	3.6
Singapore Thai	3.5
Taiwan Siraya	2.9
Taiwan Pazeh	1.8
India Mumbai Marathas	1.2
South Korea pop 3	1.1
Taiwan Puyuma	1.0
Taiwan Saisiat	1.0
China Beijing	0.8
Brazil	0.7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

HLA-B46

Dark Red = 7% or greater
Red = 3 to 7%
Orange = 1 to 3%
Green = O to 1%
Black = regions not typed

HLA-B46 (B46) is an HLA-B serotype. The serotype identifies the gene products of HLA-B*4601 allele. B*4601 resulted from a rare, interlocus, gene conversion between B62, probably B*1501, and a HLA-C allele. B*4601 is the most common HLA-B allele that does not have an origin within Africa, and estimated 400 million people in Eastern Asia carry a B46 allele. When found B*4601 segregates with only 2 HLA-Cw alleles, A limited number of HLA-A and HLA-DRB1 alleles suggesting that the allele recently expanded from a limited sized group within SE Asia. Extremely low frequencies outside of Eastern Asia are indicators of a recent expansion of B46 from a recently small population. The frequency distribution suggests the ancestral B46 population was in SE China, or, potentially Burma (Myanmar or Laos, untested). B46 in Asia correlates with wet-rice farming. The exceptions are notable, it has been found in the Nivkhi on north-eastern Sakalin Island, the Ainu, and the Nivkhi-related (genetically) Tlinglet population of Alaska at trace levels.

History of Paddy Field Cultivation: Archaeologists generally accept that wet-field cultivation originated in China. At Caoxieshan, a site of the Neolithic Majiabang culture (馬家浜文化), archaeologists excavated paddy fields. Some archaeologists claim that Caoxieshan may date to 4000-3000 BC, but as of now the oldest excavated rice paddy field dated by absolute scientific dating techniques are from Korea. There is archaeological evidence that unhusked rice was stored for the military and for burial with the deceased from the Neolithic period to the Han Dynasty in China.

Paddy field farming goes back thousands of years in Korea. A pit-house at the Daecheon-ni site yielded carbonized rice grains and radiocarbon dates indicating that rice cultivation in dry-fields may have begun as early as the Middle Jeulmun Pottery Period (c. 3500-2000 BC) in the Korean Peninsula. Ancient paddy fields have been carefully unearthed in Korea by institutes such as Kyungnam University Museum (KUM) of Masan. They excavated paddy field features at the Geumcheon-ni Site near Miryang, South Gyeongsang Province. The paddy field feature was found next to a pit-house that is dated to the latter part of the Early Mumun Pottery Period (c. 1100-850 BC). KUM has conducted excavations that have revealed similarly dated paddy field features at Yaeum-dong and Okhyeon in modern-day Ulsan.

Mumun Period rice farmers used all of the elements that are present in today's paddy fields such terracing, bunds, canals, and small reservoirs. We can grasp some paddy-field farming techniques of the Middle Mumun (c. 850-550 BC) from the well-preserved wooden tools excavated from archaeological rice fields at the Majeon-ni Site. However, iron tools for paddy-field farming were not introduced until sometime after 200 BC. The spatial scale of paddy-fields increased with the regular use of iron tools in the Three Kingdoms of Korea Period (c. AD 300/400-668).

The first paddy fields in Japan date to the Early Yayoi period. The Early Yayoi has been re-dated and thus it appears that wet-field agriculture developed at approximately the same time as in the Korean peninsula.

In the Philippines, the use of rice paddies can be traced to prehistoric times, as evidenced in the names of towns such as Pila, Laguna, whose name can be traced to the straight mounds of dirt that form the boundaries of the rice paddy, or "Pilapil."

Wet rice cultivation in Vietnam dates back to the Neolithic Hoa Binh culture and Bac Son culture.

 

HLA B*4601
Frequencies

Population	(%)
Buyei (China)	21.6
Miao (China)	18.4
Han (2) (Yunnan, China)	17.9
Thai (in Singapore)	17.2
Southern Chinese (in Taiwan)	17.2
Chinese (in Hong Kong)	16.3
Hakka (2)(Taiwan)	15.6
Guangzhou (China)	15.5
Northeastern Thailand	15.1
Minnan (Avg 1 & 2) (Taiwan)	15.0
Middle' Chinese (in Taiwan)	15.0
Hakka (Taiwan)	13.6
Wuhan (China)	13.5
Maonan (Guangxi , China)	13.4
Chinese (in Singapore)	13.4
Vietnamese	13.2
Southern Han (China)	11.5
Shanghai (China)	11.2
Meizhou Han (Guangdong, China)	10.0
Shijiazhuang Tianjian Han (Beijing)	9.6
Guangzhou Han (China)	9.4
Thailand	9.2
Nu (Yunnan, China)	9.0
Northern Chinese (in Taiwan)	8.6
Pazeh (Taiwan)	8.2
Aichi (Japan)	7.6
Lisu (Yunnan, China)	7.2
Beijing (China)	6.8
Naxi (Yunnan, China)	6.1
Hui (Qinghai, China)	5.9
Northern Han (China)	5.7
Japan (3)	5.0
Hyogo (Japan)	4.7
South Korea (3)	4.4
Man (Harbin City, China)	4.1
Siraya (Taiwan)	3.9
Central Japan	3.6
Linqu County (Shandong, China)	3.3
Timorese	2.6
Inner Mongolia (China)	2.0
Javanese (in Singapore)	2.0
Oold (Mongolia)	1.9
Nivkhi (Sakhalin I, Russia) sland	1.9
Thao (Taiwan)	1.7
Riau Malay (in Singapore)	1.5
Tuva (2) (Russia)	1.4
Tibetan (China)	1.3
Khalkh (Ulaanbaatar, Mongolia)	1.2
Ainu (Hokkaidō, Japan)	1.0
Indigenous (Taiwan)	0.9
Khalkha (Mongolia)	0.5
Brahui (Pakistan)	0.5

 

A2-Cw11(1)-B46: Because of the numbers of people represented by the sample groups, and its relative high frequency in those group A2-B46 is one of the most frequent, if not the most frequent A-B haplotype in the world, even though it is absent from the indigenous populations of most peoples in the world.

The most common haplotype, and probably the ancestral haplotype given its distribution from the Ninhivet to Indonesia is:

A*0207 : C*0102 : B*4601 : DRB1*0901 : DQA1*0302 : DQB1*0303

A different haplotype that is more common in Korea and Japan is

A*0207 : C*0102 : B*4601 : DRB1*0803 : DQA1*0103 : DQB1*0601

B46, or a closely linked allele may have been under positive selection in rice farmers of Asia.

 

HLA A2-B46 Haplotype Frequencies

Population	(%)
Buyi	16.6
Miao	13.6
Singapore (Chinese)	11.4
Chaoshan	10.1
Southern Han	7.8
VietNam	7.8
Thai	7.2
Thai Chinese	4.0
Japanese	3.3
Li	3.0
Korea	2.8
Uygar	2.7
Manchu	2.6
Inner Mongia	1.9
Northern Han	1.8

 

* Association of the HLA A2-B46-DR9 Haplotype With Autoimmune Thyroid Dysfunction After Bone Marrow Transplantation in Chinese Patients by Au WY, et al.

Abstract: Autoimmune thyroid disease (AITD) may occur in patients after bone marrow transplantation (BMT). At a median follow-up of 4 years, among 194 allografts and 28 autografts, four patients (three allografts, one autograft) developed AITD. All carried the human leucocyte antigen (HLA) A2-B46-DR9 haplotype, strongly associated with AITD in the Chinese population. No significant thyroid disorder was detected in 190 patients without this haplotype. The frequency of AITD in BMT patients with the HLA A2-B46-DR9 haplotype was 12.5%, with a relative risk of 7.8 times that of non-carriers (P < 0.001). The risk of AITD should be recognized in recipients with high-risk HLA haplotypes, and regular screening might be warranted.

 

* Distribution and co-occurrence of MHC class I, II, and III markers in southern Chinese: implications for autoimmune disease by Hawkins BR, et al.

Abstract: A study of MHC class I, II, and III markers in a group of southern Chinese in Hong Kong is reported. HLA antigen frequencies and complement allele frequencies are given, together with statistically significant pair-wise co-occurrences. Over half of the statistically significant positive and negative linkage disequilibria relate to two extended haplotypes. These haplotypes, or components of them, are associated with a number of diseases in Chinese, particularly diseases of autoimmune origin. One haplotype, A2, Bw46, DRw9, appears to be an analogue of the haplotype A1, B8, DR3 which predisposes to similar diseases in Caucasians. The question is raised of why susceptibility to the same group of diseases in two different racial groups should be related to the haplotypes having the strongest linkage disequilibria within those racial groups.

 

HLA A1-B8-DR3-DQ2 haplotype (Also: AH8.1, COX, Super B8, ancestral MHC 8.1 or 8.1 ancestral haplotype) is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6 (not to be confused with the HLA-DQ heterodimer DQ8.1). A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles, common multigene haplotypes are generally the result of descent by common ancestry (share a recent common ancestor for that segment of the chromosome).

The haplotype can be written in an extended form covering the major histocompatibility loci as follows:

HLA A*0101 : Cw*0701 : B*0801 : DRB1*0301 : DQA1*0501 : DQB1*0201 or shorthand A1::DQ2

A1::DQ2's origin is difficult to trace, suggestions of a common ancestor in Iberia or Africa have been put forward. Although its place of origin is not certain there is agreement that bearers of the European AH8.1 bear a haplotype related by a common descent.

Studies indicate that A1::DQ2 prominence is likely due to positive selection in the pre-Neolithic period and isolation in countries were wheat was not a prominent cereal. Outside of DR3-DQ2 with known associations to autoimmune disease, other factors within A1::DQ2 are believed to also contribute to autoimmune disease. Also a dozen inflammatory diseases of the immune system can attribute some risk to the haplotype. Some disease like coeliac disease primarily associate with certain genes. While other diseases, like type 1 diabetes may have several, highly different, genes that attribute risk. Still other diseases, like myasthenia gravis have undetermined linkage to the haplotype.

 

HLA-A2

HLA-A2 (A2) is a human leukocyte antigen serotype within HLA-A "A" serotype group. The serotype is determined by the antibody recognition of α2 subset of HLA-A α-chains. For A2, the alpha "A" chain are encoded by the HLA-A*02 allele group and the β-chain are encoded by B2M locus. A2 and A*02 are almost synonymous in meaning. A2 is more common in Northern Asia and North America than elsewhere, and it is part of a several long haplotypes.

The serotype identifies the gene products of many HLA-A*02 alleles, including HLA-A*0201, *0202, *0203, *0206, and *0207 gene products. A*02 is globally common, but A*0201 is at high frequencies in Northern Asia and North America. A2 is the most diverse serotype, showing diversity in Eastern Africa and Southwest Asia. While the frequency of A*0201 in Northern Asia is high, its diversity is limited to A*0201 the less common Asian variants A*0203, A*0206.

 

HLA A*0203 Frequencies

Study population	(in %)
China Guangxi Maonan	17.6
China Yunnan Lisu	15.2
Thailand Northeast	12.2
China South Han	10.8
China Guangzhou	9.8
Singapore Javanese Indone…	9.0
China Yunnan Nu	8.2
Thailand	7.7
Taiwan Minnan pop 1	6.4
Taiwan Puyuma	6.0
Taiwan Siraya	5.9
Singapore Riau Malay	5.2
India Khandesh Pawra	5.0
India West Bhils	5.0
Taiwan Pazeh	4.5
India Mumbai Marathas	3.7
Taiwan Hakka	3.6
China North Han	2.4
Sri Lanka Colombo Sinhale…	2.4
China Qinghai Hui	2.3
Burkina Faso Rimaibe	1.1
Taiwan Saisiat	1.0

HLA A*0206 Frequencies

Study population	(in %)
Pakistan Kalash	21.6
Japan Ainu Hokkaido	20.0
Japan Okinawa Ryukuan	18.3
American Samoa	13.0
Taiwan Puyuma	12.0
Taiwan Atayal	9.4
Japan pop3	8.7
Japan pop5	8.4
India North Delhi	7.7
Japan Central	7.7
Taiwan Bunun	7.4
China North Han	7.1
South Korea pop 3	7.1
Russia Tuva pop 2	6.9
Pakistan Burusho	6.0
Taiwan Taroko	5.5
Singapore Chinese Han	5.2
China Beijing	4.8
China Beijing Shijiazhuan…	4.7
Hong Kong Chinese	4.7
China Guangxi Maonan	4.6
Mongolia Buriat	4.3
China Guangzhou	4.0
Philippines Ivatan	4.0
Singapore Chinese	4.0
Taiwan Pazeh	3.6
China South Han	3.5
Taiwan Thao	3.3
Pakistan Sindhi	3.2
Pakistan Pathan	3.1
India New Delhi	3.0
Taiwan Rukai	3.0
India North Hindus	2.9
Taiwan Minnan pop 1	2.9
Taiwan Paiwan	2.9
India Andhra Pradesh Goll…	2.8
Taiwan Hakka	2.7
Papua New Guinea Eastern …	2.6
Thailand	2.5
Sri Lanka Colombo Sinhale…	2.4
Pakistan Brahui	2.3
Papua New Guinea Wanigela	2.1
Singapore Javanese Indone…	2.0
Singapore Riau Malay	2.0
Singapore Thai	2.0
Taiwan Saisiat	2.0
Taiwan Siraya	2.0
Pakistan Baloch	1.6
Taiwan Ami	1.5
Iran Baloch	1.1
Pakistan Karachi Parsi	1.1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

HLA A*0201 Frequencies

Study population	(in %)
Finland	34.4
Georgia Tibilisi Georgian…	31.0
Bulgaria	30.0
Philippines Ivatan	30.0
Spain Catalonia Girona	29.9
Portugal North	29.3
Italy North pop 1	28.9
Italy Bergamo	28.0
Czech Republic	27.4
Ireland Northern	27.4
Spain Basque Gipuzkoa Pro…	27.0
Belgium	26.6
Croatia	26.3
Australia New South Wales	26.1
Portugal Centre	26.0
Turkey (1)	25.7
Romanian	25.0
Ireland South	24.6
China Tibet	21.8
Oman	21.6
Georgia Svaneti Svans	21.3
Iran Baloch	20.2
Japan Ainu Hokkaido	20.0
China Beijing	18.7
Morocco Nador Berber	17.8
Australia Indig. Cape Yor…	17.5
Tunisia	17.5
South Korea (3)	16.5
Mongolia Buriat	14.3
Burkina Faso Rimaibe	13.8
Jordan Amman	13.4
Japan (3)	11.6
India Tamil Nadu Nadar	10.7
Japan Okinawa Ryukuan	10.2
Georgia Tibilisi Kurds	8.3
Singapore Riau Malay	6.5
India North Hindus	5.8
Taiwan Hakka	5.5
Taiwan Pazeh	5.5
China South Han	5.3
Sri Lanka Colombo Sinhale…	4.9
China Guangxi Maonan	4.6
Singapore Javanese Indone…	4.0
Taiwan Paiwan	3.9
India Andhra Pradesh Goll…	3.4
Singapore Thai	3.1
Taiwan Rukai	3.0
Taiwan Tsou	2.9
Pakistan Karachi Parsi	2.8
Taiwan Ami	2.6
New Caledonia	2.4
PNG Wanigela	2.1
Taiwan Puyuma	2.0
Taiwan Tao	2.0
India Mumbai Marathas	1.9
Thailand	1.8

HLA A*0207 frequencies

Study population	(in %)
Thailand Northeast	15.7
China Guangxi Maonan	13.4
Hong Kong Chinese	13.1
Singapore Chinese	13.1
Singapore Thai	12.2
Singapore Chinese Han	11.6
Taiwan Minnan pop 1	11.3
Thailand	10.9
China South Han	9.4
China Guangzhou	9.3
China Yunnan Nu	8.2
Taiwan Hakka	8.2
Taiwan Siraya	6.9
China Beijing	6.7
Taiwan Pazeh	6.4
China North Han	4.3
China Qinghai Hui	3.6
Japan (3)	3.4
South Korea (3)	3.0
China Inner Mongolia	2.5
China Yunnan Lisu	2.2
Mongolia Buriat	2.1
Singapore Riau Malay	2.0
Taiwan Thao	1.7
China Tibet Autonomous Re…	1.6
Russia Tuva pop 2	1.6
Burkina Faso Fulani	1.0
Japan Ainu Hokkaido	1.0
Singapore Javanese Indone…	1.0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

* HLA-A2 Allelic Microvariants in Nasopharyngeal Carcinoma by E. C. Ren, et al.

Abstract: HLA-A2-positive nasopharyngeal carcinoma (NPC; n = 38) and normal control (n = 51) populations were analysed by high-resolution oligotyping to identify A2 allelic microvariants. Within the control group, A*0207 was found to be the most common allele, accounting for 50% of the A2 frequency in normals. In contrast, this allele was found to be present in only 23% of NPC cases, suggesting a protective effect. Of these 9 NPC patients with A*0207, all were associated with B46, unlike in the control group, where it can be found associated with non-B46 antigens. Another allele, A*0201, which was thought to be protective against NPC was in fact present in 39.5% of NPC patients, more than twice the frequency in controls. These data confirm that A*0201 is not a protective allele for NPC, and other factors such as the A*0207, non-B46 haplotype are of greater importance.

 

* Association of HLA Class I and II Alleles and Extended Haplotypes With Nasopharyngeal Carcinoma in Taiwan by Hildesheim A, et al.

Abstract

Background: Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC.

Methods: We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase I, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred.

Results: We found a consistent association between HLA-A*0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A*0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B*4601, which is in linkage disequilibrium with HLA-A*0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A*0207 and HLA-B*4601 (OR = 2.8, 95% CI = 1.7 to 4.4). Individuals homozygous for HLA-A*1101 had decreased risks for NPC (OR = 0.24, 95% CI = 0.13 to 0.46). The extended haplotype HLA-A*3303-B*5801/2-DRB1*0301-DQB1*0201/2-DPB1*0401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4).

Conclusions: The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group.

 

HLA-A33

HLA-A33 (A33) shows two different distributions that can be discriminated by subtyping capability of SSP-PCR.

A*3301 distribution: The first distribution appears to have a Western distribution that introgresses into Europe as a result of the Post-neolithic periods. It is commonly found in linkage disequilibration within the A*3301-Cw*0802-B*1402 haplotype which can be extended to DRB1 and DQB1 in certain instances(See Below). The source of its general expansion appears to be the Middle Eeast or the Levant, as it is found in the Palestinian population. B14 splits into B64 (B*1401) and B65 (B*1402) but the only Arabian people which show both antigens are the United Arab Emirates.

A*3303 distribution: Certain alleles confound population histories. At the top of that list is A*3303. This allele appears to jump, literally, out of West Africa into South Asia. The point of origin is Africa, most likely central or western Africa given the low levels in East Africa (although much of East Africa is undersampled). In certain tested populations of the Middle East the leve of A*3303 is either very low, or non-existent. Within East Africa Sudan appears to be the highest at around 2%. The frequency of A*3303 begins to rise in eastern Arabia (Oman, UAE) and then markedly rise in the Brahui and Balochi of Pakistan. One haplotype stands out, the A33-B58-DR3-DQ2 haplotype which is found in West Africa, in Sudan, and Pakistan, scattered along West Indias coast, the Turkic republics and appears to have recently introgressed into Korea (post-Yayoi period of Japan) and China. So recent arrival into Asia that the level of HLA DR3-DQ2 in Korea of 2.9%. Korea is the major recent source of Japanese genes, by the Yayoi period that lasted from 3000 to 1600 years ago approximately 3/4ths of Japanese genetic makeup is attributed to this migration. And yet there is trace DR3-DQ2 in Japanese, none in the Ainu nor many other indigeonous Siberian groups.

 

HLA-DQ2

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains 2 common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

DQ2 is most common in Western Europe, North and West Africa. Highest frequencies are observed in parts of Spain and Ireland, this distribution correlates with the frequency of two of the most prevalent autoimmune diseases. There is also a increase in DQB1*0201 in Central Asia, peaking in Kazakhstan and declining slowly east to west into China and finally Southeast Asia. DQA1*0501 : DQB1*0201. DQ2.5 is one of the most predisposing factors for autoimmune disease. DQ2.5 is encoded, often, by a haplotype associated with a large number of diseases. This haplotype, HLA A1-B8-DR3-DQ2 is associated with diseases in which HLA-DQ2 has suspect involvement. Direct involvement of DQ2 is certain in coeliac disease.

 

HLA DR3-DQ2

HLA DR3-DQ2 is double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes.

The frequency of both diseases changes with respect to both the environment (diet) and the frequency of the DR3-DQ2. With coeliac disease risk is increased with the consumption of Triticeae glutens, and this also increases risk in juvenile diabetes whereas other cereals also appear to play a role. More importantly the risk of disease is greatest in homozygotes and linear increases in haplotype resulting in several fold increases of disease risk. This increased risk is most prominent in a rare cancer, enteropathy associated T-cell lymphoma. HLA-DR3-DQ2 is found in HLA A1-B8-DR3-DQ2 haplotype in Northern Europeans (including the British Ilse, Ireland, Iceland).

HLA DR3-DQ2 is not spread evenly in the among humans. It is has a substantially higher frequency in the western world, except indigenous Native American (see tables). It is virtually absent in some Asian populations. It current world distribution suggest that it spread from Africa with a wave that spread late in human evolution which reached central Asia more recently, a possibility is that it spread with agrarian cultures that migrated from Africa. [Note some population test DR3 or DQA1:DQB1, the DR3-DQ2 serotype is generally synonymous in frequency with DQ2.5]

Based on frequencies in Central and East Asia, DR3-DQ2 appears to have spread eastward recently. Of particular interest to the West African/Central Asian comparison, not only is DQ3-DQ2.5 elevated in both places, but a linked HLA A-B haplotype, A33-B58, is found in West Africans and both the A33 and B58 alleles show more allelic and haplotype diversity in West Africa. This similarity would be remarkable if this haplotype came with migrations 50,000 to 130,000 years ago, since considerable equilibration and long range migrations are expected over this time frame. Ironically, there is no convincing route of travel between West Africa and Central Asia suggested by gene frequencies in the peoples between the two. This recent migation hypothesis is supported by HLA-A36 which shows a similar African/Central Asian bimodal distribution. One population that might have been related to this migration are non-caucasians of northern Africa.

DR3-DQ2 is notably higher in W. Mongolia, Kazakhstan and W. China. One eastern haplotype is "A33-B58" and has some punctuated distribution in Western Europe at relatively low levels, and is also in extreme disequilibrium where it is found, elsewhere. In Thailand it is elevated, particularly in the Thai Chinese, but in the south and most parts of Indonesia its frequency is zero. Elevated DR3-DQ2 levels in the Muong suggest a similar North to South spread.

DR3-DQ2 presence in the Koreans and lack thereof in the Japanese suggest a recent spread into Western Pacific Rim of Asia. By HLA, Y chromosome, or mitochondrial DNA the Japanese are about 60-85% of post-Jōmon period Korean origin, and the level of DR3-DQ2 in Japanese is about 1/10 that of Koreans suggesting that DR3-DQ2 did not spread in the Yayoi (300 BC to 300 AD) and that it spread recently with Mongol spread in Eastern Asia, it is rare both east and south of China (except in regions with strong historic migrations of Chinese), rare in Indigenous Austronesians, and isolated Indigeonous American groups.

 

DR3 and DQ2.5 Levels in Asians ( %)

Population	DR3	DRB1 0301	Haplo. DR3DQ2	Estimated DQ2.5
Kazakh	13.1			13.1
Uygar (China)	14.0		12.6	12.6
Tsaatan (Mongolia)	12.5			12.5
Khalka (Mongolia)	9.0		11.5	11.5
Australo (N.S.Wales)			11.4	11.4
Iranian	10.0		10.0	10.0
Muong (Viet Nam)	12.7		9.8	9.8
Oold (Mongolia)			8.7	8.7
Jing (China)			8.1	8.1
N.W. Han (China)	7.6		7.6	7.6
Mansi (Russia)		7.4	7.4	7.4
N.India	7.4		7.4	7.4
Iran (Yadz)	5.4		5.4	5.4
Hanoi (Viet Nam)	4.4		4.0	4.0
Buryat (Siberia)		4.0	4.0	4.0
Shangdong (China)			3.6	3.6
Korean		2.9	2.9	2.9
Nusa Ten. (Indonesia)		2.4	2.4	2.4
Ulchi		1.4	1.4	1.4
Ryūkyū (Japan)	0.0		0.0	0.0
Japanese		0.7	0.3	0.3
Ainu (Japan)		0.0	0.0	0.0
ket (Russia)	0.0		0.0	0.0
Ngasan (Siberia)	0.0		0.0	0.0
Negidal (Siberia)		0.0	0.0	0.0
Molacca (Indonesia)		0.0	0.0	0.0

 

* The Origin of Minnan & Hakka, the So-Called "Taiwanese" Inferred by HLA Study by M. Lin, et al.

Abstract: The Minnan and Hakka people groups, the so-called "Taiwanese", are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai-Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggest that this haplotype is the most well conserved ancient haplotype of the Yueh.

 

HLA Gene Frenquencies in Minnan and Hakka

Population	DRB1*03	DQB1*02
Minnan	7.4	8.8
Hakka	8.6	10.6

 

HLA-B58 (B58) is involved in allopurinol sensitive drug induced Stevens-Johnson syndrome. Allopurinol is a frequent cause of severe cutaneous adverse reactions, including drug-hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis (SJS/TEN). The association with allopurinol sensitivity in JSJ/TEN was extremely strong in Asia, and somewhat less associated in Europeans.

 

A33-Cw3-B58-DR3-DQ2: Within Eastern Asia A*3303 is in linkage dissiquilbrium with one haplotype in particular, the specific genetic makeup is:

A*3303 : C*0302 : B*5801 : DRB1*0301 : DQA1*0501 : DQB1*0201

It is interesting that the Cw allele in the Pakistani population is the same as the allele in the east Asian population C*0302. 8.3 of 11.1% of the A33-B58 in the Baloch Pakistani can is linked to DR3 and presumbably DQ2.5 (There are few exceptions outside of Africa). This extends a haplotype the forms a semicircle around the Indian subcontinent indicating a subsantive and relatively recent genetic relationship. The parsis of Pakistan lack A33-B58, as with groups to the far west of Pakistan. The A33-B58-DR3-DQ2 haplotype appears to have originated in whole from West Africa, with current possibilities for Sudan or Northern Ethiopia as points of exit from Africa and a migration by the Indian ocean to the western side of the Indus River.

 

HLA A*33-B58 Frequencies

Population	(%)
Chinese (Thailand)	12.6
Baloch (Pakistan)	11.1
Chaoshan (China)	8.1
Chinese (Singapore)	5.5
Burusho (Pakistan)	4.6
Hui	4.0
Mongolian	3.7
Kalash (Pakistan)	3.6
Korea	3.5
Yaku	3.2
Panthan (Pakistan)	3.0
Tribals (India)	3.0
Baloch (SE Iran)	2.9
Brahui (Pakistan)	2.9
Southern Han	2.8
Thais	2.5
Vietnamese	2.3
Inner Mongolian	2.2
Miao	2.1
Oman	1.6
Sindhi (Pakistan)	1.5
Manchu	1.2

 

 

The Baloch (بلوچ) is an ethnic group that inhabits the region of Balochistan in the southeast corner of the Iranian plateau in Southwest Asia, including parts of Iran, Afghanistan, and Pakistan.

The Baloch speak Balochi, an Iranian language. They mainly inhabit mountainous terrains, which have allowed them to maintain a distinct cultural identity and resist domination by neighbouring rulers. Some 60 percent of the total Baloch population live in Pakistan. About 25 percent inhabit the contiguous region of southeastern Iran. In Pakistan the Balochi people are divided into two groups, the Sulaimani and the Makrani, separated from each other by a compact block of Brahui tribes.

There are different viewpoints about the origins of the Balochs, including Arabs, Turks, Iranis, and Italians who migrated to Balochistan with Alexander The Great and did not return back.

L. M. Dames says that Balochs are ancestral Irani, who migrated from the southern coastline of the Caspian Sea. L. W. Oshanen, a well-known anthropologist of the Soviet Union, has supported Dames' theory. The northern and southern Baloch, however, consider themselves of Arab descent, and Aleppo their first homeland. There is no doubt that Baloch tribes, particularly Bugti, and Rind, joined the Balochis during wars in Baloch regions, so there were many Arabs in that area at the time. To this viewpoint that Balochis are Arabs, Rai Bahadur Hetoraam also agrees and identifies them as descendants of Hazrat Ameer Hamza, uncle of Hazrat Muhammad.

 

The Burusho or Brusho people live in the Hunza, Nagar, and Yasin valleys of Gilgit Baltistan. They are predominantly Muslims. Their language, Burushaski, has not been shown to be related to any other.

The Hunza people, or Hunzakuts, descend from the principality of Hunza. They live alongside the Wakhi and the Shina. The Wakhi reside in the upper part of Hunza locally called Gojal. Wakhis also inhabit the bordering regions of China, Tajikstan and Afghanistan and also live in Gizar and Chitral district of Pakistan. The Shina-speaking people live in the southern part of Hunza. They have come from Chilas, Gilgit, and other Shina language -speaking areas of Pakistan. The Hunzas are Shia Ismaili Muslims. DNA research groups the male ancestry of the Hunza with speakers of Pamir languages (Afghans) and the Sinte Romani (Gypsies). However, they have also an East Asian genetic contribution, suggesting that at least some of their ancestry originates north of the Himalayas.

Burusho legend maintains that they descend from the village of Baltir, which had been founded by a soldier left behind from the army of Alexander the Great—a legend common to much of Afghanistan and northern Pakistan. However, genetic evidence supports only a very small, 2% Greek genetic component and that also among the Pashtun ethnic group of Pakistan and Afghanistan, not the Burusho.

 

A Kalash Man

Two Kalash Women

The Kalash or Kalasha, are an ethnic group of the Hindu Kush mountain range, residing in the Chitral district of the North-West Frontier Province of Pakistan. They speak the Kalash language, a member of the Dardic family of Indo-Aryan Languages.

They are related to the Nuristani people of the adjacent Nuristan province of Afghanistan, formerly known as Kafiristan.

Genetic Origin: Some in the academic community have speculated that the Kalash might be from ancient Middle Eastern populations, an indigenous population from South Asia, or members of Alexander the Great's army. Though often overstated, instances of blond hair or light eyes are not uncommon.

In a 2005 study of ASPM gene variants, Mekel-Bobrov et al. found that the Kalash people of Pakistan have among the highest rate of the newly-evolved ASPM haplogroup D, at 60% occurrence of the approximately 6,000-year-old allele.

The Kalash also have been shown to exhibit the exceedingly rare 19 allele value at autosomal marker D9S1120 at a frequency higher than the majority of other world populations which do have it.

Firasat et al. (2006) conclude that the Kalash lack typical Greek haplogroups (e.g. haplogroup 21), On the other hand, a study by Qamar et al. (2002) found that even though "no support for a Greek origin of their Y chromosomes was found" in the Kalash, Greek y-chromosome admixture could be as high as 20% to 40%. Considering the apparent absence of haplogroup 21 in the local population, one of the possibilities suggested was because of genetic drift. On the basis of Y chromosome allele frequency, some researchers describe the exact Greek contribution to Kalash as unclear.

Another study with Qasim Ayub, and S. Qasim Mehdi, and led by Quintana-Murci claims that "the western Eurasian presence in the Kalash population reaches a frequency of 100%, the most prevalent [mtDNA] haplogroup being U4, (pre-HV)1, U2e, and J2," and that they show "no detectable East or South Asian lineages. The outlying genetic position is seen in all analyses. Moreover, although this population is composed of western Eurasian lineages, the most prevalent ... are rare or absent in the surrounding populations and usually characterize populations from Eastern Europe, the Middle East and the Caucasus... All these observations bear witness to the strong effects of genetic drift of the Kalash population... However, a western Eurasian origin for this population is likely, in view of their maternal lineages, which can ultimately be traced back to the Middle East".

The estimates by Qamar et al. of Greek admixture has been dismissed by Toomas Kivisild et al. (2003): “some admixture models and programs that exist are not always adequate and realistic estimators of gene flow between populations ... this is particularly the case when markers are used that do not have enough restrictive power to determine the source populations ... or when there are more than two parental populations. In that case, a simplistic model using two parental populations would show a bias towards overestimating admixture”.

The study came to the conclusion that the Pakistani Kalash population estimate by (Qamar et al. 2002) “is unrealistic and is likely also driven by the low marker resolution that pooled southern and western Asian–specific Y-chromosome haplogroup H together with European-specific haplogroup I, into an uninformative polyphyletic cluster 2”.

A genetic study published in the American Journal of Human Genetics by Sengupta et al. (2006), found the Kalash to comprise high frequencies of Haplogroup L3 (25%), R1a (20%), H1* (20%), Haplogroup G2a (20%), R* (5%), J2a and J2b2 at (5%) each. Haplogroup L originates from prehistoric South Asia.

A study by Rosenberg et al. (2006) employing genetic testing among the Kalash population concluded that they are, in fact, a distinct (and perhaps aboriginal) population with only minor contributions from outside peoples. In one cluster analysis with (K = 7), the Kalash formed one cluster, the others being Africans, Europeans/Middle Easterners/South Asians, East Asians, Melanesians, and Native Americans.

In the recent study: "Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation (2008)", geneticists using more than 650,000 single nucleotide polymorphisms (SNP) samples from the Human Genome Diversity Panel, found deep rooted lineages that could be distinguished in the Kalash. The results showed them not only to be distinct, but perfectly clustered within the Central/South Asian populations at (K = 7). The study also showed the Kalash to be a separated group, with having no membership within European populations.

 

* Extreme mtDNA Homogeneity in Continental Asian Populations by Hiroki Oota, et al.

Population Tree, Showing mtDNA Homogeneity in Asia

Tw (Taiwan Han Chinese) Ca (Cantonese) - Finns - Kirghiz Lowlander - British - Kazakh - Turks - Basques - Sardinian

Tw (Taiwan Han Chinese) Ca (Cantonese) - Finns - Indian - Ainu - Aboriginal Australian - Anatolia Turks - Borneo

Tw (Taiwan Han Chinese) Ca (Cantonese) - Korean - Philippines - Uighurs - Changsha - Taiwanese (aborigines) - Vietnamese - Vanuata - Indonesian - PNG

Tw (Taiwan Han Chinese) Ca (Cantonese) - Xi'an - Tottori (Japanese) - Kirghiz Highlander - Mongolian - Ngoebe - Altai of Siberia - Amerind - Argentina - Siberians

_________________________________________________________________

 

Tunisia

 

* Diet, Living Conditions and Nasopharyngeal Carcinoma in Tunisia—A case-control study by D. Jeannel, et al.

Abstract: We conducted a case-control study of nasopharyngeal carcinoma (NPC) in Tunisia, on diet, dietary patterns and life style, the characteristics of which had been defined by an anthropological study. Eighty incident cases, diagnosed in Tunisia between November 1986 and November 1987, were each matched for sex, age and place of residence to 2 controls. The subjects were asked for dietary data referring to the year preceding the diagnosis of NPC and, with help of their families, during childhood and after weaning. After adjustment for an empirical living conditions score, the following food items were found to be associated with an increased risk for NPC: preserved spiced meat (quaddid), basic stewing preparation (mixture of red and black pepper, garlic, oil, caraway and coriander), and harissa (red pepper, olive oil, garlic, caraway, salt) taken with bread as a snack during childhood and youth. Moreover, subjects who had been directly weaned from mother's milk on to an adult diet were found to be at higher risk for NPC.

 

* HLA Association With Nasopharyngeal Carcinoma in Southern Tunisia by Hafedh Makni, et al.

Abstract: In order to study the association of HLA-A, -B and/or DRB1, DQB1 and the nasopharyngeal carcinoma (NPC), 141 patients affected with NPC were typed for the HLA class I by serology method of microlymphocytotoxicity. Among these patients 101 were genotyped for HLA class II system by the PCR-SSP technique. HLA typing results were compared to those of 116 controls. We found that the HLA-A31 and -A33 antigens were significantly more expressed in patients than in the controls (P = 0.016 and 0.010, respectively) and the HLA-A19 antigen, was significantly more frequent in patients when compared to the controls (P = 0.007). The HLA-DRB1*03 and DRB1*13 alleles were significantly more frequent in patients as compared to the controls. The DRB1*01 allele was expressed with a frequency of 20.69% in the controls whereas it was only detected in 3.96% of the NPC patients. Furthermore, the DQB1*05 allele was expressed at a frequency which was significantly less important in affected patient (P = 0.03), whereas, the DQB1*02 allele was more frequent in patients (P = 0.643 × 10−4). Thus our study revealed a significant increase of HLA-A31, A33, A19, B16, B53 and DRB1*03, DRB1*13 and DQB1*02 alleles in our patients. These markers could play a predisposing role in the development of NPC. In contrast, a decrease of HLA-B14, -B35 and DRB1*01 and DQB1*05 alleles was found suggesting a likely protective effect.

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Causes of Nasopharyngeal Carcinoma

 

* The Enigmatic Epidemiology of Nasopharyngeal Carcinoma by Ellen T. Chang, et al.

Proposed Causal Model of Endemic (types II and III) NPC

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* Occupational Exposure to Wood, Formaldehyde, and Solvents and Risk of Nasopharyngeal Carcinoma by Allan Hildesheim, et al.

Abstract: Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (>90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type 1 (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% CI = 1.0–3.0). Those exposed to wood dust for >10 years had an adjusted RR of 2.4 (95% CI = 1.1–5.0; ptrend = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93–2.2). Those exposed to formaldehyde for >10 years had an adjusted RR of 1.6 (95% CI = 0.91–2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2–5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86–1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis.

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* Increased Morbidity from Nasopharyngeal Carcinoma and Chronic Pharyngitis or Sinusitis Among Workers at a Newspaper Printing Company by Y-H Liu, et al.

Abstract

Objectives: To determine the association between printing works and nasopharygeal carcinoma as well as other diseases.

Methods: Demographic data were obtained for those who had worked in a particular newspaper company since its establishment in 1950. Through access to the data bank of the hospital records of the Labor Insurance Bureau for 1985–94, all workers were identified who had been admitted to hospital during their employment in the newspaper company. Multiple logistic regressions were performed to estimate the adjusted morbidity odds ratio (OR) for various diseases among the printing workers with cardiovascular diseases as the reference diseases. Biopsy specimens from patients with nasopharyngeal carcinoma were all subjected to in situ hybridisation of Epstein-Barr virus (EBV), and colocalisation of EBV and secretor component protein.

Results: Of the 1564 people who had worked in this company, 579 of them were admitted to hospital at least once. Five out of 144 printing workers admitted to hospital were diagnosed with nasopharyngeal carcinoma compared with none of the other 435 non-printing workers admitted to hospital. The morbidity OR for nasopharyngeal carcinoma in printing workers was 57.0 (95% confidence interval (95% CI) 2.8 to 1155.3). The morbidity OR for benign skin tumours was 28.0 (95% CI 2.7 to 293.1). Chronic pharyngitis or sinusitis also showed significant relations with printing works with a morbidity OR 29.4 (95% CI 1.7 to 514.7). Using all other diseases as the reference diseases for calculation of morbidity ORs still showed a similar trend. In situ hybridisation of EBV encoded small nuclear RNA-1 (EBER-1) showed tumour cells free of the EBV in each biopsy specimen. Colocalisation of EBER-1 and secretor component showed that some tumour cells contained both secretor component and EBV signal in each case.

Conclusion: Printing works are associated with an increased risk of nasopharyngeal carcinoma, benign skin tumours, chronic pharyngitis or sinusitis, chronic liver diseases, and mechanical injuries. Induction of the development of nasopharyngeal carcinoma is probably not related to EBV infection in these patients.

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* Cigarette Smoking, Alcohol Consumption and Risk of Nasopharyngeal Carcinoma in Taiwan by Cheng YJ, et al.

Abstract

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is rare in most countries but occurs with relatively high frequency among southern Chinese populations throughout the world. A case-control study of NPC was conducted in Taiwan to investigate the importance of active and passive cigarette exposure and alcohol consumption as risk factors for this disease.

METHODS: 375 histologically confirmed incident NPC cases (99% response rate) were prospectively identified from two hospitals in Taipei between July 1991 and December 1994 and administered a detailed questionnaire. 327 healthy community controls individually matched to cases on sex, age and residence were selected (88% response rate).

RESULTS: After multivariate adjustment, the odds ratio (OR) and 95% confidence interval (CI) was 1.7 (1.1-2.9 with p = 0.03 for increasing dose-response) for those who smoked for > or = 25 years compared with non-smokers. Passive smoking during childhood or adult life was not associated with an increased risk of disease. Alcohol consumption was not associated with NPC risk. The OR for subjects with > or = 15 grams of ethanol per day compared to non-drinkers was 1.1 (95% CI = 0.7-1.7).

CONCLUSIONS: Our results suggest that long term cigarette smoking is associated with NPC but that low level exposure to cigarette smoke via passive exposure and alcohol consumption are not associated with disease risk.

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* Evaluation of Risk Factors for Nasopharyngeal Carcinoma in High-risk Nasopharyngeal Carcinoma Families in Taiwan by Yang XR, et al.

Abstract: A study of nasopharyngeal carcinoma (NPC) families with two or more affected members was conducted in Taiwan (265 families with 2,444 individuals, 502 affected and 1,942 unaffected) to determine the association between NPC and potential etiologic factors in NPC high-risk families. Similar to results from a previous case-control study in Taiwan, Guangdong salted fish consumption during childhood, exposure to wood, and betel nut consumption were all associated with elevated NPC risk using conditional logistic regression, although these associations were not as strong as in the case-control study possibly due to shared environment among family members. Risk associated with cumulative wood exposure and salted fish consumption before age 10 was stronger in families with early NPC age-onset [odds ratio (OR(wood)), 5.10; 95% confidence interval (95% CI), 1.50-17.34; OR(fish), 3.94; 95% CI, 1.47-10.55] or three or more affected members (OR(wood), 4.41; 95% CI, 1.58-12.30; OR(fish), 4.27; 95% CI, 1.10-16.47). In contrast, a tendency for elevated risk was noted for betel nut use in late age-onset families (OR, 2.44; 95% CI, 1.16-5.13) and the CYP2E1 c2 allele in families with less than three affected members (OR, 2.06; 95% CI, 1.04-3.35). Risk estimates associated with these exposures were similar when the analyses were restricted to EBV-seropositive subjects. To better adjust for degree of relationship among family members and residual genetic correlations, we also calculated ORs using a variance components model. The results from the two methods were similar indicating that the risk estimates from conditional logistic regression were unbiased.

 

Betel Nut

Areca Nut and Betel Leaf Consumption in the World

The Areca nut is the seed of the Areca palm (Areca catechu), which grows in much of the tropical Pacific, Asia, and parts of east Africa. It is commonly referred to as "betel nut" as it is often chewed wrapped in betel leaves.

Chewing the mixture of areca nut and betel leaf is a tradition, custom or ritual which dates back thousands of years from South Asia to the Pacific. It constitutes an important and popular cultural activity in many Asian and Oceanic countries, including India, Pakistan, Sri Lanka, Papua New Guinea, Bangladesh, Bhutan, Taiwan, Myanmar, Cambodia, the Solomon Islands, Thailand, Laos, the Maldives, Palau, and Vietnam. It is not known how and when the areca nut and the betel leaf were combined together into one psychoactive drug. Archaeological evidence from Thailand, Indonesia and the Philippines suggests that they have been used in tandem for four thousand years or more.

Effects on health: The International Agency for Research on Cancer (IARC) regards the chewing of betel and areca nut to be a known human carcinogen. The media has reported that regular chewers of betel leaf and areca nut have a higher risk of damaging their gums and acquiring cancer of the mouth, pharynx, esophagus and stomach. Studies have found tobacco and caustic lime increase the risk of cancer from areca nut preparations.

Studies exist of the use of a "pure" paan preparation: areca nut, betel leaf, and lime. One study found that unprocessed areca nuts, at high doses, displayed a very weak carcinogenicity. In contrast, since 1971 many studies have found areca nut extracts to cause cancer in rodents. In 2003 the International Agency for Research on Cancer (IARC) reached the conclusion that there is sufficient evidence that the habit of chewing betel quid with or without tobacco is carcinogenic to humans. Support is provided by a recent study which found that paan without tobacco is a risk factor for oral cancer. They found paan with and without tobacco increased oral cancer risk by 9.9 and 8.4 times respectively.

Chewing areca nut alone has been linked to oral submucosal fibrosis.

According to Medline Plus, "Long-term use has been associated with oral submucosal fibrosis (OSF), pre-cancerous oral lesions and squamous cell carcinoma. Acute effects of betel chewing include asthma exacerbation, hypertension, and tachycardia. There may be a higher risk of cancers of the liver, mouth, esophagus, stomach, prostate, cervix, and lung with regular betel use. Other effects can include a possible effect on blood sugar levels, possibly increasing the risk of type 2 diabetes.

 

 

* Difference in the Incidence Trend of Nasopharyngeal and Oropharyngeal Carcinomas in Taiwan: Implication from Age-Period-Cohort Analysis by Chiun Hsu, et al.

Excerpt: This study showed a significant difference in the incidence trends of nasopharyngeal and oropharyngeal carcinomas in Taiwan. The incidence of nasopharyngeal carcinoma continues to decrease in younger birth cohorts, and this trend seems more prominent in women than in men. By contrast, the incidence of oropharyngeal carcinoma increases much more rapidly in men than in women. Our data from the age-period-cohort analysis suggest that lifestyle factors play an important role in these trends.

Modulation of lifestyle has been considered a key way to prevent cancers. Change in cancer incidence due to modulation of lifestyle is most likely reflected in cohort effect. A notable example is gastric cancer, in which cohort effect was found accountable for its decreasing incidence. The decreasing incidence of gastric cancer was found to be related to the increased use of refrigerators, improved sanitation, and decreased consumption of preserved food. Preserved food and the potential carcinogens, such as nitrosamine, in it have also been regarded as an important risk factor for nasopharyngeal carcinoma. The westernization of lifestyle in Taiwan took place after World War II, which was coincident with the continuing decrease in nasopharyngeal carcinoma risk for birth cohorts 1936 to 1945 and onwards in our study. Our data further illustrate the importance of environmental and lifestyle factors on the pathogenesis of nasopharyngeal carcinoma found in previous migrant studies. Westernization of lifestyle may influence the incidence trend of other cancers in Taiwan. For example, a shift in the incidence and age distribution pattern of female breast cancer in Taiwanese toward that of Caucasian Americans have been noted, and a strong cohort effect on this trend has been shown.

Both environmental and host factors may play a role in the difference of nasopharyngeal carcinoma incidence trend between men and women found in this study. However, such as difference was not found in Hong Kong. Because the population of Taiwan and Hong Kong had the same ethnic background, and because the composition of both populations remains relatively stationary in the past decades, environmental and lifestyle factors may be more important in accounting for the difference. Men in Taiwan may have greater exposure to other risk factors of nasopharyngeal carcinoma, thus negated the effect of westernization of lifestyle. For example, the prevalence rates of tobacco smoking and betel quid chewing were at least 10-fold higher in men than in women. Besides, men may be more susceptible than women to environmental insults. Evidence suggested that men had a higher level of the cytochrome P450 2E1 (CYP2E1) activity than women. Genetic polymorphism of CYP2E1 enzyme has been found to be a determinant of nasopharyngeal carcinoma risk, and the CYP2E1 variant with a higher metabolic activity and thus a higher ability to activate carcinogens was associated with higher risk of nasopharyngeal carcinoma. It is also possible that the beneficial effects of lifestyle change on nasopharyngeal carcinoma risk involve factors that have differential effects between men and women.

Decrease in incidence of nasopharyngeal carcinoma has been found only in populations with high endemic incidence. Lee et al. compared the incidence trend of nasopharyngeal carcinoma in Hong Kong, Singapore, United States, England, and Australia. Nasopharyngeal carcinoma incidence decreased only in Hong Kong, whereas the incidence in other countries remained stationary. However, analysis of the Chinese population in Singapore suggested that a decrease of nasopharyngeal carcinoma incidence may occur since mid-1990s. Cox et al. studied the incidence trend of oral cancers in New Zealand, a country with a low incidence of nasopharyngeal carcinoma (about 0.8%), from 1957 to 1991 and showed a cohort effect for the increase in incidence of both nasopharyngeal carcinoma and other head and neck carcinomas. In addition to differences in genetic background, diet and other environmental factors may account for the different incidence trends.

The incidence of oropharyngeal carcinoma in Taiwan rose rapidly in the last two decades, and betel quid use, which is popular as a stimulant and as a social etiquette, seemed to be the most prominent risk factor. Betel quid consumption has been shown to be an important risk factor for various cancers in the upper aerodigestive tract, and the risk for oropharyngeal carcinoma and precancerous lesions, including oral leukoplakia and submucosal fibrosis, increased with increasing amount and duration of betel quid use. The increase in oropharyngeal carcinoma incidence in Taiwan closely paralleled the increase in the estimated per capita consumption of betel quid. Besides, the incidence increased more significantly for intraoral (including lip and mouth) sites, areas with more direct exposure to carcinogens in betel quid than for pharyngeal (including oropharynx and hypopharynx) sites. These evidences support the notion that betel quid consumption is the most prominent risk factor for the rise of oropharyngeal carcinoma incidence. The much stronger cohort effect for men on the relative risk of oropharyngeal carcinoma may also reflect the male predominance of betel quid use.

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鼻咽癌

鼻咽癌（NPC, Nasopharyngeal carcinoma）是一種發生於鼻咽腔或上咽喉部的癌症。在世界的某些地區，例如東南亞和非洲，患此病的人比其他地方多，主要是由於膳食和遺傳因素的影響。

病因: 鼻咽癌在微觀主要分為三類，角化性癌（keratinizing型），非角化性癌（non-keratinizing型）及未分化型。

家族因素: 家族中若有人罹患鼻咽癌，則家族內其他人的罹病機率也增加，特別是一等親的直系親屬。

生活及環境因素

• 經常食用醃漬或煙燻食物：鼻咽癌好發於華人和愛斯基摩人，罹病機率遠高於歐美及日韓等民族，而中國東南沿海及台灣等地的居民罹病機率又高於中國北方，特別是廣東地區，因此又有「廣東癌」之稱。即使是遷居海外的華僑，其罹病機率仍較當地人來得高。一般認為這和鹹魚的食用有密切聯繫，因為鹹魚含有致癌物亞硝胺。
• 抽煙
• 長期吸入刺激性物質，例如工業用的石綿、鉻、鎳等
• 工作場所不通風

EB病毒: 研究顯示鼻咽癌病人血清中的抗EB病毒抗體的種類及含量均高於一般人，而大部份中國南方的人均有EB病毒的接觸史，雖然大部份人在一生中都不會發病，但有小部份人在接觸特殊的外來環境，使體內的免疫系統與EB病毒產生特殊反應而發病。至於EB病毒導致鼻咽癌發病的基制仍待進一步研究。

其他

• 男性罹病機率高出女性三倍。
• 有鼻竇炎病史者罹病機率也較一般人高。

症狀

注意：下列症狀並不一定能作為診斷罹患鼻咽癌的依據，下列症狀也無法包括所有可能的罹病徵兆。

• 頭頸部腫大
• 單側耳塞
• 持續性耳鳴、聽力障礙
• 單側鼻塞或鼻涕增多
• 頭痛（單側、兩側、偏頭痛）
• 早晨起床後痰或鼻涕中帶有血絲
• 口鼻不明原因滲血
• 鼻腔蓄膿
• 眼球內斜、複視、視力模糊
• 臉部知覺麻痺

檢查方式

• 抽血
• 鼻咽內視鏡
• 鼻咽抹片
• 組織切片
• 細針抽吸穿刺(Fine Needle Aspiration, FNA)
• 電腦掃描（CT）
• 核磁共振（MRI）

治療方式

• 放射線治療：鼻咽癌對放射線極為敏感，被公認為早期治療最有效的方式。
• 化學治療：多用於已發生遠端轉移的晚期病患。
• 外科手術：用於摘除經照射後仍未消除的頸部淋巴腺，屬輔助性療法。
• 同時合併放射線治療與化學治療：在放射線治療的同時進行化學治療可以增加治療成功率。部分病人在接受化學治療後，使腫瘤縮小，再合併放射線治療，也有較過去進步的成功率。

配合適當的治療，非keratinizing型和未分化型鼻咽癌，五年存活率約65 ％。至於keratinizing型鼻咽癌，治療則較困難，這是由於癌細胞對放射線有較大抵抗性。