Original article 417 Tagging single nucleotide polymorphisms in excision repair cross-complementing group 1 (ERCC1) and risk of primary lung cancer in a Chinese population Hongxia Ma a,* , Liang Xu b,* , Jing Yuan d , Minhua Shao c , Zhibin Hu a , Feng Wang d , Yi Wang c , Wentao Yuan b , Ji Qian c , Ying Wang b , Pengcheng Xun a , Hongliang Liu c , Weihong Chen d , Lin Yang b , Guangfu Jin a , Xiang Huo a , Feng Chen a , Yin Yao Shugart e , Li Jin b,c , Qingyi Wei f , Tangchun Wu d , Hongbing Shen a , Wei Huang b and Daru Lu c Background and objective Low nucleotide excision repair (NER) capacity has been associated with increased risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is one of the NER core enzymes, and polymorphisms in ERCC1 may lead to altered repair function of the enzyme and therefore confer predisposition to cancer. The goal of this study was to test the hypothesis that common variants in ERCC1 were associated with lung cancer risk. Methods The genotyping analyses for 7 selected single nucleotide polymorphisms in ERCC1 using the TaqMan assay was conducted in a case–control study of 1010 patients with incident lung cancer and 1011 cancer-free controls in a Chinese population. Results We found that the variant genotypes of the rs3212948 C allele were associated with significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.73 (95% CI = 0.60–0.88) for CG; 0.96 (95% CI = 0.65–1.41) for CC and 0.76 (95% CI = 0.63–0.91) for CG/CC, compared with the GG genotype]. Similarly, a significant protective effect was also evident for the variant genotypes of rs1007616 C/T [adjusted OR = 0.72 (95% CI = 0.59–0.89) for CT; 0.90 (95% CI = 0.61–1.35) for TT and 0.75 (95% CI = 0.62–0.91) for CT/TT, compared with the CC genotype]. Stratified analysis revealed that the protective effects of these 2 single nucleotide polymorphisms were both more evident among young patients and patients without family history of cancer. Consistently, when assessing each unique haplotype compared with the most common haplotype ‘TAGCACG’, lung cancer risk was significantly decreased among patients who carried the haplotype ‘TCCCATT’ with the variant rs3212948C and rs1007616T alleles (P value = 0.0340, P-sim = 0.0325, adjusted OR = 0.78; 95% CI = 0.63–0.97). Conclusion These findings indicate that ERCC1 polymorphisms may contribute to the etiology of lung cancer. Further functional studies were warranted to elucidate the mechanism of the associations. Pharmacogenetics and Genomics 17:417–423  c 2007 Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2007, 17:417–423 Keywords: case–control study, DNA repair, genetic susceptibility, haplotype, molecular epidemiology a Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing, b Department of Genetics, Chinese National Human Genome Center at Shanghai, c State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, d Institute of Occupational Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, e Epidemiology Department, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland and f Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA Correspondence to Professor Daru Lu, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Handan Rd., Shanghai 200433, China Tel/fax: + 86 21 65642799; e-mail: drlu@fudan.edu.cn *Ma H. and Xu L. contributed equally to this work. Received 9 January 2006 Accepted 10 August 2006 Introduction Cellular DNA is routinely damaged by endogenous or exogenous mutagens such as ultraviolet light, tobacco smoke, and reactive oxygen species [1,2]. DNA damage must be repaired to enable the cell to maintain genomic integrity [3]. Alternatively, unrepaired DNA damage can accumulate, resulting in apoptosis or leading to unregu- lated cell growth and carcinogenesis [2]. Complex pathways involving numerous enzymes to perform nucleotide excision repair (NER) is a major cellular defense mechanism against DNA damage from bulky DNA adducts induced by chemical carcinogens, such as polycyclic aromatic hydrocarbons from tobacco smoke [4]. Studies have shown that impaired DRC (DNA repair capacity) is associated with increased risk of smoking- related lung cancer [5,6]. 1744-6872  c 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.