Genetic Polymorphisms Involved in Carcinogen Metabolism and DNA Repair and Lung Cancer Risk in a Japanese Population
Genetic Polymorphisms Involved in Carcinogen Metabolism and DNA Repair and Lung Cancer Risk in a Japanese Population
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DOI：
10.1097/jto.0b013e31824de30f
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发表时间：
2012-06-01
影响因子：
20.4
通讯作者：
Nakanishi, Yoichi
中科院分区：
文献类型：
--
作者：
Kiyohara, Chikako;Horiuchi, Takahiko;Nakanishi, Yoichi
背景：肺癌发生、致癌物代谢和DNA修复途径的几个组成部分可能与肺癌的个体遗传易感性有关。方法：在一项病例对照研究中，我们评估了细胞色素P450 1A1 rs4646903和rs104894、谷胱甘肽S转移酶M1和谷胱甘肽转移酶1缺失多态、GSTP1rs1695、X射线修复、切除修复交叉互补组2(ERCC2rs13181)、补充中国仓鼠缺陷的rs25487和XRCC3rs861539在日本人群中的作用。结果：CYP1A1 rs4646903(OR=1.72，95%CI=1.25-2.38)，rs1048943(OR=1.40，95%CI=1.02-1.92)，GSTM1缺失多态(OR=1.38，95%CI=1.01-1.89)，GSTP1 rs1695(OR=1.48，95%CI=1.04-2.11)，ERCC2 rs13181(OR=1.89，95%CI=1.28~2.78)和中国仓鼠1rs25487(OR=1.54，95%CI=1.12~2.13)与肺癌风险相关，而GSTT1缺失多态和XRCC3 rs861539与肺癌风险无关。CYP1A1 rs4646903、GSTM1缺失多态和ERCC2 rs13181多个高危基因的相关组合使肺癌的风险增加5.94倍(95%CI=2.77~12.7)。结论：多个高危基因的相关组合可发现高危人群。有必要进行进一步的研究来验证我们的发现。
Background: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer.Methods: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI).Results: CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25-2.38), rs1048943 (OR = 1.40, 95% CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01-1.89), GSTP1 rs1695 (OR = 1.48, 95% CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer.Conclusions: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.