The nucleotide excision repair (NER) pathway plays an important role in removal of tobacco-caused DNA lesions, and single nucleotide polymorphisms (SNPs) of the genes in this pathway are good candidates for investigating susceptibility to smoking-related lung cancer. Using a candidate gene approach combined with linkage disequilibrium analysis, we selected and genotyped 37 tagging SNPs of 7 core NER genes by using TaqMan high throughput genotyping assay in a case-control study of 1010 incident lung cancer patients and 1011 cancer-free controls in a Chinese population. Variant alleles in four SNPs (2 in ERCC1, 1 in ERCC4/XPF and 1 in XPC) were associated with a significant decreased lung cancer risk in the single locus analysis. In the combined analyses with the above four SNPs, the risk of lung cancer was significantly decreased as the numbers of variant alleles increased. Furthermore, we found that the haplotypes distributions of individual gene between the cases and the controls were significantly different for ERCC5/XPG (P = 0.0035), XPA (P = 0.0177) and XPC (P = 0.0066). Haplotype ERCC1 TCGCGCT was associated with significantly decreased risk for lung cancer when compared with the most common haplotype. These results from this Chinese population provide preliminary evidence to support that genetic variants in the NER pathway may jointly contribute to individual susceptibility to lung cancer.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]