No association between the XPD 312, 751, or XRCC1 399 polymorphisms and K-ras gene mutation in smoking non-small-cell lung cancer.

Lung cancer is strongly associated with exposure to tobacco smoke (1–3). Mutations in the K-ras gene have been found in 20–35% of lung adenocarcinomas of smokers (4–8), compared with about 5–7% in those of nonsmokers (7, 8), suggesting that their formation may be associated with exposure to tobacco smoke carcinogens. DNA repair helps preserve the integrity of the cellular genome by repairing DNA damage induced by tobacco smoke carcinogens (9). Some polymorphic variants of DNA repair genes, such as the nucleotide excision repair gene xeroderma pigmentosum group D (XPD) polymorphisms at codons 312 and 751, and the base excision repair X-ray repair cross-complementing group 1 (XRCC1) polymorphism at codon 399, have been associated with an increased risk of lung cancer (10–13). In addition, our recent study showed that lung cancer cases who were smokers and carried the XPD 312 Asp/ Asp genotype had a higher incidence of p53 mutations in their lung tumors (14). In the present study, we analyzed K-ras mutations in lung tumors of these same lung cancer cases and investigated the relationship between the presence of these mutations and the status of DNA repair polymorphism, specifically the XPD Asp312Asn, XPD Lys751G1n, and XRCC1 Arg399Gln genotypes, of the cases.