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Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer

M. Soledad Marín^1,, M. Felicitas López-Cima¹, Laura García-Castro¹, Teresa Pascual², Manuel G. Marrón³ and Adonina Tardón¹

¹ Department of Medicine, Oncology Institute (Molecular Epidemiology Unit of the Oncology Institute), Oviedo University, Oviedo (Asturias), Spain; ² Pneumology Section, Cabueñes Hospital, Gijón (Asturias), Spain; and ³ Pneumology Section, San Agustín Hospital, Avilés (Asturias), Spain

Requests for reprints: Adonina Tardón, Department of Medicine, Oncology Institute (Molecular Epidemiology Unit of the Oncology Institute), Oviedo University, Edificio Santiago Gascón, 33006 Oviedo (Asturias), Spain. Phone: 34-98-5103556; Fax: 34-98-5106276. E-mail: atardon{at}uniovi.es

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.

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