女性肺癌易感性与DNA修复基因多态性

目的 研究非吸烟女性群体中DNA修复基因XRCC1 (X-ray repair complementing defective repair in Chi-nese hamster cell1)同义突变多态与肺癌遗传易感性.方法 选择肿瘤医院55例非吸烟女性肺癌患者,74名正常对照者进行PCR-限制性片段长度多态性 (RFLP)分型,分析XRCC1 Pro206Pro和G ln632Gln多态/单体型与肺癌的关联.结果 XRCC1 Pro206Pro (G)变异等位基因携带者与AA野生等位基因纯合子个体相比较,肺癌发生风险为3.93倍 (OR=3.93,95% CI=1.47~10.52,P<0.004);单体型在肺癌组与对照组之间的总体分布差异有统计学意义 (P=0.005);由2个同义突变等位基因结合的单体型1[Pro206Pro (G)-G ln632Gln (A)]是高风险性单体型 (OR=4.04,95% CI=1.36~11.96,P=0.007);2个多态之间存在强烈的连锁不平衡 (D'=0.702).结论 非吸烟女性群体中,XRCC1 Rro206Pro (G)等位基因及含其等位基因的单体型可能是肺癌易感性的重要因素.

Polymorphisms of DNA repair gene XRCC1 Pro206Pro and Gln632Gln and genetic susceptibility of lung cancer among non-smoking Chinese women

Objective To assess the relationship between the polymorphisms of DNA repair gene XRCC1 Pro206Pr and Gln632Gln and susceptibility of lung cancer among non-smoking Chinese women.Methods A hospital-based case-control study consisting of 55 newly diagnosed and previously untreated subjects with lung cancer and 74 cancer-free control subjects matched on age (±3 years),gender and ethnicity was conducted.All subjects were unrelated ethnic Han Chinese and lifetime non-smoking women from northeastern China.Genotypes were determined by PCR-RFLP method.Results Variant G-allele of XRCC1 Pro206Pro was significantly over-represented in lung cancer patients (G versus A,OR=3.69,95% CI=1.46-9.34,P=0.004).Carriers of the variant G-allele of Pro206Pro were at significantly increased risk of lung cancer (AG+GG versus AA,OR=3.93,95% CI=1.47-10.52,P=0.004).No significant effect was observed for polymorphism of XRCC1 Gln632Gln.Overall haplotype distribution was significant different between cases and controls (P=0.005).Hapolotype (Pro206Pro (G)-Gln632Gln (A)) defined by combination of variant alleles in the two polymorphisms was a high-risk haplotype of lung cancer susceptibility (OR=4.04,95% CI=1.36-11.96,P=0.007).The two polymorphisms were in strong linkage disequilibrium (D'=0.702).Conclusion The present results are consistent with our previous findings that variant G-allele of DNA repair gene XRCC1 Pro206Pro or a haplotype encompassing it's alleles may be an important susceptibility factor in the process of lung cancer developonent in non-smoking Chinese women.Larger sample studies will be required further to validate these findings.