Genetic Polymorphism of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) and Their Correlation with Risk of Lung Cancer in a Chinese Population

• Published in: Archives of medical research Vol. 42; no. 3; pp. 226 - 234
• Main Authors: Li, Zheng, Guan, Wei, Li, Meng-xia, Zhong, Zhao-yang, Qian, Cheng-yuan, Yang, Xue-qin, Liao, Ling, Li, Zeng-peng, Wang, Dong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2011
• Subjects: Adenocarcinoma - genetics; Amino Acid Substitution; Asian Continental Ancestry Group; Base excision repair; Carcinoma, Small Cell - genetics; Carcinoma, Squamous Cell - genetics; Case-Control Studies; DNA Glycosylases - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-Binding Proteins - genetics; Female; Gene Frequency; Genetic Association Studies; Genetic susceptibility; Genetic variant; Genotype; Humans; Indexing in process; Internal Medicine; Logistic Models; Lung cancer; Lung Neoplasms - genetics; Male; Middle Aged; Molecular epidemiology; Multivariate Analysis; Odds Ratio; Polymorphism, Genetic; Sequence Analysis, DNA; Smoking; X-ray Repair Cross Complementing Protein 1; Molecular epidemiology; Genetic susceptibility; Base excision repair; Genetic variant; Lung cancer
• ISSN: 0188-4409; 1873-5487
• DOI: 10.1016/j.arcmed.2011.04.005

Background and Aims Reactive oxygen species (ROS) and numerous carcinogens may cause DNA damage including oxidative base lesions that contribute to the risk of lung cancer. The base excision repair (BER) pathway could effectively remove oxidative lesions in which 8-oxoguanine glycosylase-1 (OGG1), x-ray repair cross-complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease 1 (APE1) play key roles. The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer. Methods In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and −141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models. Results Individuals homozygous for the variants APE1 −141GG showed a protective effect for lung cancer overall (OR = 0.62; 95% CI: 0.42–0.91; p  = 0.02) and for lung adenocarcinoma (OR = 0.65; 95% CI, 0.44–0.96; p  = 0.03). When analyzing the combined effects of variant alleles, 84 patients and controls were identified who were homozygous for two or three of the potential protective alleles (i.e., OGG1 326Cys, XRCC1 399Gln and APE1 −141G). ORs were significantly reduced when all patients were analyzed (OR = 0.62; 95% CI: 0.38–0.99; p  = 0.05). Conclusions The combined effects of polymorphisms within BER genes may contribute to the tumorigenesis of lung cancer.