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Nasopharyngeal carcinoma (NPC) is a serious health problems in the southern Chinese population, with an incidence rate ranging from 15 to 50 per 100 000.1 NPC is an epithelial malignancy with a striking racial and geographic distribution differences.2 High incidence rates are observed in the southeast Chinese population, and similar rates have been reported in these people wherever they have migrated, including Singapore,3 Taiwan,4 and Hong Kong.5 These incidence rates are almost 100 fold higher than in white populations.2 The marked racial and geographic differences in NPC susceptibility are considered a multifactorial and polygenic event with environmental and genetic components and correlation with Epstein-Barr virus infection.2,6–10
Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders. Thus, the hope of resolving the genetic aetiology of NPC and the mechanisms of racial and geographic differences in NPC susceptibility has prompted a search for genetic variants in gene candidates thought to play a role in the pathogenesis of the NPC. A genetic linkage study based on affected sibling pairs collected from different Chinese populations in southeast Asia, which located the susceptibility locus to within the 6p22 region, supported the involvement of the human leukocyte antigens (HLA) in the pathogenesis of NPC.11 Recently, two genomewide searches, carried out in 20 Cantonese speaking families from Guangdong province and 18 families from Hunan province in southern China, provided evidences of susceptibility loci for NPC on chromosome 4p15.1-q12 and 3p21.31–21.2, respectively.12,13 Case–control studies have established associations between specific HLA molecules and NPC in several populations including Asians, whites, and North Africans.14–16 In addition to the HLA, some non-HLA loci, including the heat shock protein 70-2 (HSP70-2),17 cyclin D1 (CCND1),18 glutathione S-transferase M1 (GSTM1 …
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