State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Cancer Res. 2011 Apr 15;71(8):3000-8. doi: 10.1158/0008-5472.CAN-10-0469. Epub 2011 Mar 2.
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 2-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 P(trend) < 0.01 were identified. Seven of these SNPs were located within 3 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 P(combined) of 5.55 × 10(-5), with OR = 1.20 (95% CI = 1.10-1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong linkage disequilibrium with rs927220 (r(2) = 0.7), had a significant P(combined) 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.
DNA 修复在防止环境致癌中起着核心作用，并且已经报道 DNA 修复基因的遗传变异与几种人类恶性肿瘤有关。为了评估 DNA 基因变异是否与鼻咽癌（NPC）风险相关，在中国广东省的粤语人群中进行了一项候选基因关联研究，该人群是 NPC 风险最高的族群。采用两阶段研究设计。在发现阶段，对 88 个 DNA 修复基因的 676 个标记 SNP 进行了病例对照研究（病例/对照=755/755）的基因分型。发现 11 个 SNP 的 P(trend)<0.01。其中 7 个 SNP 位于 RAD51L1、BRCA2 和 TP53BP1 这 3 个基因内。在验证阶段，在另一个粤语人群中对这 11 个 SNP 进行了基因分型（病例/对照=1568/1297）。这两个 SNP（rs927220 和 rs11158728）都位于 RAD51L1 中，与 NPC 仍然密切相关。SNP rs927220 具有显著的 P(combined)值为 5.55×10(-5)，OR=1.20（95%CI=1.10-1.30），Bonferroni 校正后 P=0.0381。另一个 SNP(rs11158728)与 rs927220 紧密连锁不平衡（r(2)=0.7），具有显著的 P(combined)值为 2.0×10(-4)，Bonferroni 校正后 P=0.1372。基因-环境交互作用分析表明，咸鱼摄入和吸烟等暴露可能与 DNA 修复基因变异存在交互作用，但需要进一步研究。我们的研究结果支持 DNA 修复基因，特别是 RAD51L1，在 NPC 发病机制和发展中起作用的观点。
