Comprehensive pathway-based association study of DNA repair gene variants and the risk of nasopharyngeal carcinoma.
Comprehensive pathway-based association study of DNA repair gene variants and the risk of nasopharyngeal carcinoma.
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DOI：
10.1158/0008-5472.can-10-0469
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发表时间：
2011-04-15
期刊：
影响因子：
11.2
通讯作者：
Jia WH
中科院分区：
文献类型：
--
作者：
Qin HD;Shugart YY;Bei JX;Pan QH;Chen L;Feng QS;Chen LZ;Huang W;Liu JJ;Jorgensen TJ;Zeng YX;Jia WH
DNA修复在保护免受环境致癌作用中起着核心作用，并且DNA修复基因的遗传变体已被报道与几种人类恶性肿瘤相关。为了评估DNA基因变异是否与鼻咽癌（NPC）风险相关，在中国广东省的广东人群中进行了一项候选基因关联研究-鼻咽癌风险最高的种族群体。采用两阶段研究设计。在发现阶段，在匹配的病例对照研究（病例/对照= 755/755）中，对覆盖88个DNA修复基因的676个标记SNP进行基因分型。鉴定出11个P趋势<0.01的SNP。这些SNPs中的7个位于3个基因中，即RAD 51 L1、BRCA 2和TP 53 BP 1。在验证阶段，这11个SNP在一个单独的广东人群体中进行基因分型（病例/对照= 1，568/1，297）。两个SNP（rs 927220和rs 11158728）-都在RAD 51 L1-仍然与NPC密切相关。SNP rs 927220具有显著性P组合为5.55 × 10−5，OR = 1.20（95%CI = 1.10 - 1.30），Bonferroni校正P = 0.0381。另一个SNP（rs 11158728）与rs 927220（r2 = 0.7）处于强LD中，具有2.0 × 10−4的显著P组合，Bonferroni校正P = 0.1372。基因-环境交互作用分析表明，食用咸鱼和吸烟暴露与DNA修复基因变异存在潜在的交互作用，但需要进一步研究。我们的研究结果支持了DNA修复基因，特别是RAD 51 L1，在NPC病因和发展中发挥作用的观点。
DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China --the ethnic group with the highest risk for NPC. A two-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with Ptrend <0.01 were identified. Seven of these SNPs were located within three genes, RAD51L1, BRCA2 and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls = 1,568/1,297). Two of the SNPs (rs927220 and rs11158728) – both in RAD51L1 – remained strongly associated with NPC. The SNP rs927220 had a significant Pcombined of 5.55 × 10−5, with OR = 1.20 (95%CI = 1.10 to 1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong LD with rs927220 (r2 = 0.7), had a significant Pcombined of 2.0 × 10−4, Bonferroni corrected P = 0.1372. Gene-environment interaction analysis suggested that the exposures of salted-fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development.