Key Laboratory of Environment and Population Health of University in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, People's Republic of China.
Mutat Res. 2011 Aug 1;713(1-2):1-7. doi: 10.1016/j.mrfmmm.2011.05.003. Epub 2011 May 12.
DNA repair genes play a crucial role in carcinogenesis. The paper aims to explore if common variants in ERCC1 are involved in lung cancer susceptibility. A Chinese case-control study included 339 lung cancer cases and 358 controls using five haplotype-tagging SNPs (htSNPs) (rs3212980, rs3212964, rs3212961, rs11615 and rs2298881) from the HapMap database, capturing 95% of the common haplotypic diversity of ERCC1. A combined analysis of eleven htSNPs covering ERCC2 and ERCC1 was performed. No significant association between individual htSNPs and lung cancer susceptibility was observed. There were interactions between rs3212961 and rs2298881and smoking duration (P=0.03 and P=0.01, respectively). Thus, the variant alleles of rs3212961 [OR (95% CI)=1.81(1.03-3.17), P=0.04] and rs2298881 [OR (95% CI)=2.16(1.26-3.70), P=0.005] were associated with risk of lung cancer among long-term smokers (>20 years) but not among never smokers and short-term smokers. No significant associations with lung cancer susceptibility were observed for global or individual haplotypes defined by five htSNPs of ERCC1. A highly differential distribution of haplotypes based on eleven htSNPs covering ERCC2 and ERCC1 were found (global test P=4.3×10(-5)). After Bonferroni correction, haplotypeER2+1-1 [OR (95% CI)=3.63 (1.39-9.47), P=0.005, marginally] and haplotypeER2+1-8 [OR (95% CI)=4.46 (2.03-9.79), P=5.6×10(-5), strongly] were associated with increased risk of lung cancer. The diplotype analysis with haplotypeER2+1-8 was also statistically significant (P<0.001). Haplotype analysis of pathological subtypes revealed that htSNPs of both genes may mainly influence the risk of lung adenocarcinoma. Strong linkage disequilibrium exist in two regions encompassing ERCC2 and ERCC1. These data suggest that common genetic variations in ERCC1 may influence increased risk of smoking-related lung cancer and one of the causative effectors may locate around or within ERCC2.
DNA 修复基因在致癌作用中起着至关重要的作用。本文旨在探讨 ERCC1 中的常见变异是否与肺癌易感性有关。采用哈普特数据库中的 5 个单倍型标签 SNP（rs3212980、rs3212964、rs3212961、rs11615 和 rs2298881），对 339 例肺癌病例和 358 例对照进行了中国病例对照研究，这些 SNP 可捕获 ERCC1 中 95%的常见单倍型多样性。对包括 ERCC2 和 ERCC1 的 11 个 htSNPs 进行了联合分析。未观察到个体 htSNP 与肺癌易感性之间存在显著关联。rs3212961 和 rs2298881 与吸烟时间之间存在交互作用（P=0.03 和 P=0.01）。因此，rs3212961 的变异等位基因[OR（95%CI）=1.81（1.03-3.17），P=0.04]和 rs2298881 [OR（95%CI）=2.16（1.26-3.70），P=0.005]与长期吸烟者（>20 年）而非从不吸烟者和短期吸烟者的肺癌风险相关。未观察到五个 ERCC1 htSNP 定义的整体或个体单倍型与肺癌易感性有显著关联。基于涵盖 ERCC2 和 ERCC1 的 11 个 htSNPs 的单倍型发现了高度差异的分布（全局检验 P=4.3×10（-5））。经 Bonferroni 校正后，单倍型 ER2+1-1 [OR（95%CI）=3.63（1.39-9.47），P=0.005，边缘）和单倍型 ER2+1-8 [OR（95%CI）=4.46（2.03-9.79），P=5.6×10（-5），强烈]与肺癌风险增加相关。单倍型 ER2+1-8 的二倍型分析也具有统计学意义（P<0.001）。对病理亚型的单倍型分析表明，两个基因的 htSNP 可能主要影响肺腺癌的风险。ERCC2 和 ERCC1 两个区域之间存在很强的连锁不平衡。这些数据表明，ERCC1 中的常见遗传变异可能影响与吸烟相关的肺癌风险增加，其中一个致病效应因子可能位于 ERCC2 周围或内部。
