Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk
Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk
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DOI：
10.1093/carcin/bgh153
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发表时间：
2004-08-01
期刊：
影响因子：
4.7
通讯作者：
Tajima, K
中科院分区：
文献类型：
--
作者：
Ito, H;Matsuo, K;Tajima, K
APE 1（脱嘌呤/脱嘧啶核酸内切酶1）和XRCC 1（X射线交叉互补组1）是DNA修复蛋白，在碱基切除修复（BER）途径中发挥重要作用。其编码基因的多态性与DNA修复能力的改变有关，因此可能影响癌症风险。在本病例对照研究中，178例日本肺癌病例和449例年龄和性别匹配的对照，我们调查了APE 1 Asp 148 Glu，XRCC 1 Arg 399 Gln和吸烟习惯在肺癌风险中的基因-环境相互作用。使用条件logistic回归模型对结果进行分析，并根据年龄、性别和吸烟状况进行调整。APE 1 148 Asp/Asp、Asp/Glu和Glu/Glu基因型的吸烟者与不吸烟者相比，其校正比值比为3.01（95% CI 1.39-6.51，P = 0.005）、2.73（95% CI 1.29-5.77，P = 0.008）和7.33（95% CI 2.93-18.3，P < 0.001）。吸烟与APE 1 148 Glu/Glu基因型的基因-环境交互作用有统计学意义（OR 3.59，95%CI 1.28-10.1，P = 0.015）。当同时评估APE 1 Asp 148 Glu和XRCC 1 Arg 399 Gln多态性时，APE 1 148 Glu或XRCC 1 399 Gln等位基因为0-1、2和3-4的当前吸烟者与这些等位基因为0的从不吸烟者相比的校正比值比为2.96（95% CI 1.57-5.58，P = 0.001）、3.86（95% CI 1.85-8.05，P < 0.001）和6.01（95% CI 2.25-16.1，P < 0.001）。吸烟与APE 1 148 Glu或XRCC 1 399 Gln等位基因的交互作用有统计学意义（OR 2.44，95% CI 1.00-9.22，P = 0.049）。APE 1密码子148 Glu/Glu基因型与重度吸烟和轻度吸烟的基因环境交互作用OR值分别为1.04（95% CI 0.38-2.90，P = 0.936）和2.67（95% CI 1.00-7.68，P = 0.049）。这些结果表明，APE 1 Asp 148 Glu和XRCC 1 Arg 399 Gln多态性可能会改变肺癌的风险归因于吸烟暴露。
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.