女性肺癌易感性与DNA修复基因多态性  

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

作　　者：祁荣[1] 宋铁华[1] 马业罡[2] 刘峥嵘[3] 孙晓玲[4] 孙中芙[1] 尹娇杨[1] 

机构地区：[1]沈阳医学院辽宁省高校环境与人口健康重点实验室,沈阳110034 [2]辽宁省肿瘤医院胸外科 [3]辽宁省人民医院普外二科 [4]沈阳东方医疗集团菁华医院

出　　处：《中国公共卫生》2009年第7期802-804,共3页Chinese Journal of Public Health

基　　金：国家自然科学基金(30571016);辽宁省教育厅高等学校科学研究项目(A类,05L438)

摘　　要：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XRCC1Pro206Pro和Gln632Gln多态/单体型与肺癌的关联。结果XRCC1Pro206Pro（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）-Gln632Gln（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,XRCC1Rro206Pro（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。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 casecontrol 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 Hart 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 poly- morphism of XRCC1 Ghi632Gln. Overall haplotype distribution was significant different between cases and controls （ P = 0. 005）. Hapolotype （Pm206Pro[ 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）. Condusion The present results are consistent with our previous findings that variant G-allele of DNA repair gene XRCC1 Pro206Pro or a haplotypeencompassing 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.

关 键 词：DNA修复基因XRCC1 遗传多态性 肺癌 非吸烟女性 

分 类 号：R394.3[医药卫生—医学遗传学]