DNA修复基因XPA单核苷酸多态性与肺癌遗传易感性的研究

目的研究中国汉族人群核苷酸切除修复基因XPA A23G多态与肺癌遗传易感性的关系.方法采用病例-对照研究方法,以PCR-RFLP技术分析了310例经组织学确诊的肺癌病例和341例按年龄、性别频数配对的非肿瘤医院对照XPA基因A23G多态,比较不同基因型与肺癌风险的关系,并探讨不同环境因素在其中所起的影响.结果XPA基因A23G多态三种基因型在肺癌病人和对照间的分布差异具有显著性(x2=6.607,P=0.037).与携带XPA 23AA基因型者相比较,携带至少一个23G等位基因(即23GG和23AG基因型)的个体肺癌风险降低34%(校正OR=0.66,95%CI=0.44～0.98).分层分析显示,此保护作用在肿瘤家族史阳性者中尤为明显,校正OR为0.31(95%CI=0.13～0.76).结论XPA A23G多态性可能与中国汉族人群肺癌遗传易感性有关,这一相关性有待进一步的体内和体外功能学研究来证实.

The single nucleotide polymorphism in the promotor of DNA repair gene XPA and in association with the risk of lung cancer

Objective To study the relationship between one polymorphism in the promoter of the DNA repair gene XPA and the susceptibility to lung cancer in a Chinese population. Methods Genotypes were determined by the PCR-restriction fragment length polymorphism (PCR-RFLP) method in 310 histologically-confirmed lung cancer cases and 341 controls whose age and sex matched to above cases. Results The XPA A23G genotype frequencies were 27. 1 % (AA) , 42. 9% (AG) , and 30. 0% (GG) in the patient cases and 21. 1% (AA) , 52.8% (AG), and 26. 1% (GG) in the control subjects, respectively, and the difference was statistically significant (x = 6. 61, P=0. 037). Multivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele (AG+ GG genotypes) had a significantly decreased risk for lung cancer (adjusted OR= 0. 66;95%CI = 0.44-0.98) compared with the wild-type genotype (23AA). Stratified analysis showed that the protective effect was more evident in subjects with a family history of cancer. Conclusion These results suggest that the XPA A23G polymorphism may have a role in lung cancer susceptibility in this investigated population. Further studies are needed to elucidate potential functional relevance of the XPA 23G variant allele.