HapMap-based study of a region encompassing ERCC1 and ERCC2 related to lung cancer susceptibility in a Chinese population
HapMap-based study of a region encompassing ERCC1 and ERCC2 related to lung cancer susceptibility in a Chinese population
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基于 HapMap 的 ERCC1 和 ERCC2 区域与中国人群肺癌易感性相关的研究
DOI：
10.1016/j.mrfmmm.2011.05.003
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发表时间：
2011-08-01
影响因子：
2.3
通讯作者：
Song, Tiehua
中科院分区：
文献类型：
--
作者：
Yin, Jiaoyang;Vogel, Ulla;Song, Tiehua
DNA修复基因在肿瘤发生中起着至关重要的作用。本文旨在探讨ERCC 1的常见变异是否与肺癌易感性有关。一项中国病例对照研究包括339例肺癌病例和358例对照，使用来自HapMap数据库的5个单倍型标记SNP（htSNP）（rs3212980、rs3212964、rs3212961、rs 11615和rs 2298881），捕获了ERCC 1 95%的常见单倍型多样性。进行了覆盖ERCC 2和ERCC 1的11个htSNP的组合分析。未观察到个体htSNPs与肺癌易感性之间的显著关联。rs3212961和rs 2298881与吸烟时间之间存在交互作用（分别为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rs 2298881 [OR（95%CI）= 2.16（1.26-3.70），P = 0.005]与长期吸烟者（>20年）的肺癌风险相关，但与从不吸烟者和短期吸烟者无关。对于由ERCC 1的5个htSNPs定义的整体或个体单倍型，未观察到与肺癌易感性的显著关联。基于覆盖ERCC 2和ERCC 1的11个htSNP，发现了高度差异的单倍型分布（全局检验P=4.3 x 10（-5））。经Bonferroni校正后，单体型ER 2 + 1-1 [OR（95%CI）= 3.63（1.39-9.47），P=0.005，轻微]和单体型ER 2 + 1-8 [OR（95%CI）= 4.46（2.03-9.79），P = 5.6 x 10（-5），强烈]与肺癌风险增加相关。单倍型ER 2 + 1-8的双倍型分析也有统计学意义（P < 0.001）。病理亚型的单倍型分析显示，这两个基因的htSNPs可能主要影响肺腺癌的风险。在ERCC 2和ERCC 1两个区域存在较强的连锁不平衡。这些数据表明，ERCC 1的常见遗传变异可能会影响吸烟相关肺癌的风险增加，其中一个致病效应物可能位于ERCC 2周围或内部。(C)2011爱思唯尔有限公司版权所有。
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 rs2298881 and 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 x 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 x 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. (C) 2011 Elsevier B.V. All rights reserved.