DNA修复基因XPA单核苷酸多态性与肺癌遗传易感性的研究

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

目的研究中国汉族人群核苷酸切除修复基因XPAA23G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XPA23AA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XPAA23G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。

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.