Marín M Soledad, López-Cima M Felicitas, García-Castro Laura, Pascual Teresa, Marrón Manuel G, Tardón Adonina
Department of Medicine, Oncology Institute (Molecular Epidemiology Unit of the Oncology Institute), Oviedo University, Edificio Santiago Gascón, 33006 Oviedo (Asturias), Spain.
Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1788-93.
Reduced DNA repair capacity due to inherited polymorphisms may increase the susceptibility to smoking-related cancers. In this report, we investigate the relationship between xeroderma pigmentosum complementary group C poly (AT) insertion/deletion polymorphism (XPC-PAT) of the XPC gene and lung cancer risk in a hospital-based case-control study of 359 newly diagnosed lung cancer patients and 375 control subjects matched on age, sex, and catchment area. The XPC genotype was determined by PCR-RFLP, and the results were analyzed using logistic regression, adjusting for relevant covariates. We found that the frequency of the PAT+/+ genotype was higher in the cases (20.6%) than in the controls (14.1%; P = 0.057) and that the PAT+/+ subjects were at significantly increased risk for lung cancer [adjusted odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.55]. Stratified analysis revealed that the risk was higher in former smokers (OR, 2.15; 95% CI, 1.07-4.31) and older people (OR, 2.76; 95% CI, 1.02-7.51), although this probably occurs due to 63.4% of cases older than 73 years being ex-smokers. When stratified by histologic type, the variant genotype was associated with statistically significant increased risk for squamous cell carcinoma (OR, 1.93; 95% CI, 1.06-3.51). In conclusion, our findings support the hypothesis that PAT and intron 11 C/A XPC polymorphisms are linked in the Spanish population and may contribute to the risk of developing lung cancer probably due to a higher frequency of deletion of exon 12 and reduced DNA repair capacity of the XPC protein.
由于遗传多态性导致的DNA修复能力降低可能会增加患吸烟相关癌症的易感性。在本报告中，我们在一项基于医院的病例对照研究中，调查了XPC基因的着色性干皮病C互补组多聚（AT）插入/缺失多态性（XPC-PAT）与肺癌风险之间的关系，该研究纳入了359例新诊断的肺癌患者和375名在年龄、性别和集水区相匹配的对照受试者。通过PCR-RFLP确定XPC基因型，并使用逻辑回归分析结果，对相关协变量进行校正。我们发现，病例组中PAT+/+基因型的频率（20.6%）高于对照组（14.1%；P = 0.057），且PAT+/+受试者患肺癌的风险显著增加[校正优势比（OR），1.60；95%置信区间（95%CI），1.01-2.55]。分层分析显示，既往吸烟者（OR，2.15；95%CI，1.07-4.31）和老年人（OR，2.76；95%CI，1.02-7.51）的风险更高，尽管这可能是由于63.4%年龄大于73岁的病例为既往吸烟者。按组织学类型分层时，变异基因型与鳞状细胞癌风险的统计学显著增加相关（OR，1.93；95%CI，1.06-3.51）。总之，我们的研究结果支持以下假设：在西班牙人群中，PAT和内含子11 C/A XPC多态性相关，可能由于外显子12缺失频率较高和XPC蛋白的DNA修复能力降低，从而增加患肺癌的风险。
