title: Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer.
abstract: Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln have been associated with altered protein function and BER activity. This case-control study examined the contribution of these two polymorphisms, alone and in combination, or in interaction with smoking, to the risk of developing lung cancer. We estimated the risk of lung cancer associated with these polymorphisms in 1,000 cases and 1,000 cancer-free controls using logistic regression models. Subjects having the ADPRT Ala/Ala genotype had an odds ratio (OR) of 1.68 [95% confidence interval (95% CI), 1.27-2.23] compared with those having the Val/Val genotype. A greater than multiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CI) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or =16, 16 to 28, or >28 pack-years were 1.13 (0.79-1.62), 1.35 (0.68-2.70), 2.46 (1.35-4.51) or 17.09 (8.15-35.83), respectively (P trend test < 0.001). Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased risk of lung cancer in a supermultiplicative manner (OR for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, 5.91; 95% CI, 2.09-16.72), although the XRCC1 polymorphism itself was not associated with the risk. In conclusion, the ADPRT Val762Ala polymorphism plays an important role in smoking-related lung cancer and the XRCC1 Arg399Gln polymorphism may serve as a risk modifier.
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100 021, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Gang
authors.initials: G
authors.lastname: Liang
authors.forename: Bingtao
authors.initials: B
authors.lastname: Hao
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D011065:Poly(ADP-ribose) Polymerases