Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese
Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese
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DOI：
10.1002/ijc.10861
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发表时间：
2003-03-01
影响因子：
6.4
通讯作者：
Tsai, ST
中科院分区：
文献类型：
--
作者：
Lu, CC;Chen, JC;Tsai, ST
鼻咽癌是一种上皮性肿瘤，在中国南方非常普遍。大量研究表明，特定的HLA单倍型和HLA复合体中的基因与NPC相关。作为定位易感基因的第一次尝试，HLA-A、-8和-A2亚型与NPC的相关性进行了研究。与以前的报道一致，鼻咽癌患者HLA-A2的频率[OR = 2.50，pc = 0.020（研究人群）; OR = 3.73，pc = 0.0030（≥ 40岁）]显著高于健康对照组。双位点分析表明，无论是在研究人群还是在≥ 40岁人群中，A2（+）B46（+）个体比A2（-）B46（-）个体更易患鼻咽癌。然而，这可能是由于这两个基因的紧密连锁。此外，在研究人群和大于或等于40岁组中，A2（+）83（+）个体的风险高于A2（-）B38（-）个体; A2和B38没有遗传连锁。这些发现表明，B38或B46单独不能赋予鼻咽癌的高风险，但与A2，838或B46阳性结合大大增加了风险。从研究人群中鉴定的5种A2亚型与NPC均无显著相关性。分析了位于HLA-A端97 kb的微卫星标记D 6S 211与鼻咽癌的相关性。D 6S 211等位基因4与鼻咽癌的发生有显著相关性（OR = 3.97，pc = 0.0042）。这些结果强烈支持了这样的假设：HLA区域中与NPC易感性相关的基因位于HLA-A基因座内。(C)2002 Wiley-Liss，Inc.
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, -8, 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 (greater than or equal to40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2(+)B46(+) individuals are at greater risk for NPC than A2(-)B46(-) individuals in both the population studied and the greater than or equal to40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2(+)83(+) individuals were at higher risk than A2(-)B38(-) individuals in both the population studied and the greater than or equal to40-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, 838 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. (C) 2002 Wiley-Liss, Inc.