title: Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers.
abstract: The association between metabolic polymorphisms and cigarette smoking-induced cancers has been documented. However, the role of DNA repair polymorphism in carcinogenesis is less clear. To investigate if the polymorphisms of metabolic traits and DNA repair modulate smoking-related DNA damage, we used sister chromatid exchange (SCE) as a marker of genetic damage to explore the relationship of microsomal epoxide hydrolase (mEH), glutathione S-transferase M1 (GSTM1), and X-ray cross-complementing group 1 (XRCC1) and cigarette smoking-induced SCE. Sixty-one workers without significant exposure to mutagens were recruited. Questionnaires were completed to obtain detailed occupational, smoking, and medical histories. SCE frequency in peripheral lymphocytes was determined using a standard cytogenetic assay and GSTM1, mEH (exons 3 and 4), XRCC1 (codon 399) genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP). Smokers had higher SCE frequency than non-smokers (8.4 versus 7.1, P<0.05). Among workers who had smoked equal to or greater than 10 cigarettes each day, those with XRCC1 Arg/Gln+Gln/Gln had higher SCE frequency than those with XRCC1 Arg/Arg after adjusting for potential confounders (9.0 versus 7.9, P<0.05). The interaction of XRCC1 and cigarettes smoked per day on SCE frequency was also observed (P=0.02). There was no significant interaction between cigarettes smoked per day with GSTM1 and mEH on SCE frequency. Our results support previous epidemiological studies that XRCC1 may play a role in cigarette smoking-induced lung cancer.
authors.affiliation: Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, No. 1 Ren-Ai Road, Sec. 1, 10018 Taipei, ROC.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lei
authors.forename: Shing-jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Chuen-Chau
authors.initials: CC
authors.lastname: Chang
authors.forename: Hsen-Wen
authors.initials: HW
authors.lastname: Kuo
authors.forename: Jiin-Chyuan
authors.initials: JC
authors.lastname: Luo
authors.forename: Ming J W
authors.initials: MJ
authors.lastname: Chang
authors.forename: Tsun-Jen
authors.initials: TJ
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics; D005091:Exons / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012854:Sister Chromatid Exchange; D012907:Smoking; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D004851:Epoxide Hydrolases; D005819:Genetic Markers; D005982:Glutathione Transferase; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human