Single nucleotide polymorphisms of DNA repair gene XPC and risk of lung cancer in a Chinese population. Y. Bai¹, J. Yuan¹, Z. Hu², X. Yang¹, F. Wang¹, L. Xu³, M. Shao⁴, Y. Wang⁴, W. Yuan³, J. Qian⁴, H. Ma², Y. Wang³, H. Liu⁴, F. Chen², Y. Liu⁴, L. Jin⁴, Q. Wei⁵, H. Shen², D. Lu⁴, T. Wu¹. 1) Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2) Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing, China; 3) Department of Genetics, Chinese National Human Genome Center at Shanghai, Shanghai, China; 4) State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; 5) Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
   DNA repair is a major defense against environmental damage to the genome and protect the cell from carcinogenesis. In the nucleotide excision repair (NER) pathway, xeroderma pigmentosum C (XPC) repair protein participates in recognition of DNA damage and initiation of DNA repair. Polymorphisms of the XPC gene are thought to have an effect on DNA repair capacity and susceptibility to cancer. In this study, we investigated five XPC-related tagSNPs in a case-control study of 1010 patients with newly diagnosed lung cancer and 1011 controls matched on age and sex. In individual tagSNP analysis, we found that the rs3731055AG+AA genotype was associated with a significantly decreased risk of lung adenocarcinoma, but an increased risk of small cell carcinomas. Accordingly, we also found that the haplotype ACCCA was associated with decreased risk of lung adenocarcinoma, but increased the risk of small cell carcinomas, which reflected the presence of rs3731055A allele in this haplotype. Further combined analysis of all five polymorphisms, we found that compared with subjects with 0-3 risk alleles, those having 4-6 risk alleles had a significantly 1.26-fold increased risk of lung cancer, and this association was more evident in the subgroups of young peoples (age < 60), males, light smoker and patients with lung adenocarcinoma. These results suggest that the inherited variation in XPC may modulate the risk of lung cancer, especially lung adenocarcinoma.