Why are East Asians more susceptible to several infection-associated cancers (carcinomas of the nasopharynx, stomach, liver, adenocarcinoma of the lung, nasal NK/T-cell lymphomas)?
There are at least five cancers with uniquely high incidence amongst East and Southeast Asian ethnic groups - namely nasopharyngeal carcinoma (NPC); gastric carcinoma; hepatocellular carcinoma (HCC); adeno-carcinoma of the lung in female non-smokers and nasal NK/T-cell lymphomas. They all appear to be related to an infective cause (Epstein Barr Virus, Helicobacter pylori, hepatitis B virus). We hypothesize that a genetic bottleneck 30,000years ago at the Last Glacial Maximum could have resulted in unique genetic polymorphisms in Toll-like receptor 8, making East Asians more vulnerable to these infective associated cancers. This bottleneck could have been caused by the presence of malaria in the southern Himalayan conduit between central and East Asia; and only those with an attenuated innate immune response to the malarial parasite (perhaps reflected by the TLR8 polymorphism) were spared the ravages of cerebral malaria; allowing these people to cross into east Asia, but then rendering them susceptible to later endemic infections and their associated cancers.
National Cancer Centre, Singapore. trdwts@nccs.com.sg
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Wee
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Nei
K W
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Yeoh
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Yeo
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Loong
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Qian
D001210:Asia, Southeastern; D004198:Disease Susceptibility; D005260:Female; D016481:Helicobacter Infections / Q000150:complications*; D006509:Hepatitis B / Q000150:complications*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000150:complications* / Q000382:microbiology / Q000821:virology; D014412:Tumor Virus Infections / Q000150:complications*