吸烟习惯与DNA修复基因APE1 Asp148Glu和XRCC1 Arg399Gln多态性之间的基因-环境相互作用对日本肺癌风险的影响。
Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk.
作者信息
Ito Hidemi, Matsuo Keitaro, Hamajima Nobuyuki, Mitsudomi Tetsuya, Sugiura Takahiko, Saito Toshiko, Yasue Tetsuo, Lee Kyoung-Mu, Kang Daehee, Yoo Keun-Young, Sato Shigeki, Ueda Ryuzo, Tajima Kazuo
机构信息
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya Aichi, Japan.
出版信息
Carcinogenesis. 2004 Aug;25(8):1395-401. doi: 10.1093/carcin/bgh153. Epub 2004 Mar 25.
APE1 (apurinic/apyrimidinic endonuclease 1) and XRCC1 (X-ray cross-complementing group 1) are DNA repair proteins that play important roles in the base excision repair (BER) pathway. Polymorphisms in their encoding genes are associated with altered DNA repair capacity and thus may impact on cancer risk. In the present case-control study with 178 Japanese incident lung cancer cases and 449 age- and sex-matched controls, we investigated the gene-environment interaction among APE1 Asp148Glu, XRCC1 Arg399Gln and smoking habit in lung cancer risk. The results were analyzed by using conditional logistic regression models, adjusted for age, sex and smoking status. The adjusted odds ratio for the current smokers with APE1 148Asp/Asp, Asp/Glu and Glu/Glu genotype as compared with the never smokers with the Asp/Asp genotype were 3.01 (95% CI 1.39-6.51, P = 0.005), 2.73 (95% CI 1.29-5.77, P = 0.008) and 7.33 (95% CI 2.93-18.3, P < 0.001), respectively. The gene-environment interaction between current smoking and APE1 148Glu/Glu genotype was statistically significant (OR 3.59, 95% CI 1.28-10.1, P = 0.015). When APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were evaluated together, the adjusted odds ratios for the current smokers with 0-1, 2 and 3-4 of APE1 148Glu or XRCC1 399Gln alleles as compared with never smokers with the 0 of these alleles were 2.96 (95% CI 1.57-5.58, P = 0.001), 3.86 (95% CI 1.85-8.05, P < 0.001) and 6.01 (95% CI 2.25-16.1, P < 0.001), respectively. The gene-environment interaction between current smoking and three or more APE1 148Glu or XRCC1 399Gln alleles was statistically significant (OR 2.44, 95% CI 1.00-9.22, P = 0.049). The OR for the gene-environment interaction of Glu/Glu genotype of APE1 codon 148 with heavy smoking was 1.04 (95% CI 0.38-2.90, P = 0.936) and that with light smoking was 2.67 (95% CI 1.00-7.68, P = 0.049). These results suggest that APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms might modify the risk of lung cancer attributable to cigarette smoking exposure.
脱嘌呤/脱嘧啶核酸内切酶1（APE1）和X射线修复交叉互补蛋白1（XRCC1）是DNA修复蛋白，在碱基切除修复（BER）途径中发挥重要作用。其编码基因中的多态性与DNA修复能力的改变相关，因此可能影响癌症风险。在这项针对178例日本肺癌新发病例和449例年龄及性别匹配对照的病例对照研究中，我们调查了APE1 Asp148Glu、XRCC1 Arg399Gln多态性与吸烟习惯在肺癌风险中的基因-环境相互作用。采用条件逻辑回归模型对结果进行分析，并对年龄、性别和吸烟状况进行了校正。与携带Asp/Asp基因型的从不吸烟者相比，携带APE1 148Asp/Asp、Asp/Glu和Glu/Glu基因型的当前吸烟者的校正比值比分别为3.01（95%可信区间1.39 - 6.51，P = 0.005）、2.73（95%可信区间1.29 - 5.77，P = 0.008）和7.33（95%可信区间2.93 - 18.3，P < 0.001）。当前吸烟与APE1 148Glu/Glu基因型之间的基因-环境相互作用具有统计学意义（比值比3.59，95%可信区间1.28 - 10.1，P = 0.015）。当同时评估APE1 Asp148Glu和XRCC1 Arg399Gln多态性时，与携带0个这些等位基因的从不吸烟者相比，携带0 - 1个、2个以及3 - 4个APE1 148Glu或XRCC1 399Gln等位基因的当前吸烟者的校正比值比分别为2.96（95%可信区间1.57 - 5.58，P = 0.001）、3.86（95%可信区间1.85 - 8.05，P < 0.001）和6.01（95%可信区间2.25 - 16.1，P < 0.001）。当前吸烟与三个或更多APE1 148Glu或XRCC1 399Gln等位基因之间的基因-环境相互作用具有统计学意义（比值比2.44，95%可信区间1.00 - 9.22，P = 0.049）。APE1密码子148的Glu/Glu基因型与重度吸烟的基因-环境相互作用的比值比为1.04（95%可信区间0.38 - 2.90，P = 0.936），与轻度吸烟的比值比为2.67（95%可信区间1.00 - 7.68，P = 0.049）。这些结果表明，APE1 Asp148Glu和XRCC1 Arg399Gln多态性可能会改变因接触香烟烟雾而导致的肺癌风险。
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