Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population

Previous studies suggested that suboptimal DNA repair capacity is associated with cancer risk and that the Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may influence DNA repair capacity. We therefore tested the hypothesis that these two XPD polymorphisms are associated with susceptibility to lung cancer in a hospital-based, case-control study in a Chinese population. Genotypes were determined by polymerase chain reaction-based restriction fragment length polymorphism methods in 383 healthy controls and 351 patients with lung cancer. We found that those who carried at least one 312Asn variant allele had an increased risk of squamous cell carcinoma (SCC) of the lung compared with those with the 312Asp/Asp genotype (adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 1.10-2.96). Compared with those having the 751Lys/Lys genotype, subjects carrying at least one variant 751 Gln allele were at a borderline increased risk of SCC of the lung (adjusted OR, 1.52; 95% CI, 0.94-2.46). Furthermore, stratified analysis suggested a multiplicative interaction between tobacco smoking and the Asp312Asn polymorphism on risk of SCC of the lung. The adjusted ORs of SCC of the lung for the variant XPD 312Asn genotype alone, for smoking ≥29 pack-years alone, and for both the factors combined were 1.04 (95% CI, 0.37-2.94), 4.74 (95% CI, 2.88-9.49), and 14.32 (95% CI, 5.80-35.2), respectively. Similar results were evident for the Lys751Gln polymorphism that was in the linkage disequilibrium with the variant 312Asn allele. These data suggest that the two polymorphisms in the XPD gene may influence risk of smoking-related SCC of the lung.