HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in a Chinese population.
HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in a Chinese population.
复制标题
DOI：
10.1093/carcin/bgp107
复制
发表时间：
2009-07
期刊：
影响因子：
4.7
通讯作者：
Jiaoyang Yin;U. Vogel;Yegang Ma;R. Qi;Huiwen Wang
中科院分区：
文献类型：
--
作者：
Jiaoyang Yin;U. Vogel;Yegang Ma;R. Qi;Huiwen Wang
DNA修复基因被认为是潜在的癌症易感基因。鼠类切除修复交叉互补修复缺乏症，互补组2 (ERCC2)/色素性干皮病互补组D （XPD）蛋白被认为是核苷酸切除修复（NER）通路的关键酶。为了阐明常见的ERCC2变异是否与肺癌易感性相关，我们在中国人群中进行了一项病例对照研究，包括339例原发性肺癌患者和358例年龄、性别和种族匹配的对照组。对来自HapMap数据库的6个单倍型标记单核苷酸多态性（rs238403、rs50871、rs3916840、rs238415、rs3916874和rs1799787）进行分析，基本覆盖了ERCC2基因的遗传变异。虽然这6个htsnp都与肺癌风险无关，但我们发现两个ERCC2单倍型与肺癌风险相关。由rs238403T-rs50871T-rs3916840C-rs238415C-rs3916874G-rs1799787C定义的单倍型4和由rs238403C-rs50871G-rs3916840C-rs238415C-rs3916874G-rs1799787C定义的单倍型7与肺癌风险增加密切相关[比值比，OR(95%置信区间，CI) = 2.62 (1.53-4.50), P = 0.0003；OR (95% CI) = 3.01 (1.36-6.63), P = 0.004。此外，双倍型分析还强化了单倍型4 (OR （95% CI) = 3.56 (2.12-5.87), P < 0.001）或单倍型7 (OR （95% CI) = 3.38 (1.75-6.55), P < 0.001）与肺癌的显著相关性。连锁不平衡分析也证实了ERCC2中6个htsnp对之间存在相当大的连锁不平衡。这些结果表明，风险亚单倍型与一个或多个生物功能多态性共分离。我们的研究结果为ERCC2在中国人群肺癌发展中的作用提供了证据。
DNA repair genes have been proposed as candidate cancer susceptibility genes. The excision repair cross-complementing rodent repair deficiency, complementation group 2 (ERCC2)/xeroderma pigmentosum complementary group D (XPD) protein is considered to be a key enzyme in nucleotide excision repair (NER) pathway. To elucidate whether common ERCC2 variants are associated with lung cancer susceptibility, we conducted a case-control study consisting of 339 cases with primary lung cancer and 358 controls matched on age, gender and ethnicity in a Chinese population. Six haplotype tagging single-nucleotide polymorphisms (htSNPs) (rs238403, rs50871, rs3916840, rs238415, rs3916874 and rs1799787) from HapMap database were analyzed, which provide an almost complete coverage of the genetic variations in the ERCC2 gene. Although none of the six htSNPs was individually associated with lung cancer risk, we found that two ERCC2 haplotypes were associated with risk of lung cancer. Haplotype 4 defined by rs238403T-rs50871T-rs3916840C-rs238415C-rs3916874G-rs1799787C and haplotype 7 defined by rs238403C-rs50871G-rs3916840C-rs238415C-rs3916874G-rs1799787C were strongly associated with an increased risk of lung cancer [odds ratio, OR (95% confidence interval, CI) = 2.62 (1.53-4.50), P = 0.0003 for hap4; OR (95% CI) = 3.01 (1.36-6.63), P = 0.004 for hap7]. Furthermore, diplotype analyses also strengthened the significant associations of risk haplotype 4 [OR (95% CI) = 3.56 (2.12-5.87), P < 0.001] or risk haplotype 7 [OR (95% CI) = 3.38 (1.75-6.55), P < 0.001] and lung cancer. Analysis of linkage disequilibrium (LD) also confirmed that considerable LD exists between the pairs of the six htSNPs within ERCC2. These results suggested that the risk subhaplotypes cosegregate with one or more biologically functional polymorphisms. Our results provide evidence to support a role for ERCC2 in lung cancer development in a Chinese population.