TY - JOUR
T1 - Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer
AU - Zhang, Xuemei
AU - Miao, Xiaoping
AU - Liang, Gang
AU - Hao, Bingtao
AU - Wang, Yonggang
AU - Tan, Wen
AU - Li, Yi
AU - Guo, Yongli
AU - He, Fuchu
AU - Wei, Qingyi
AU - Lin, Dongxin
PY - 2005/2/1
Y1 - 2005/2/1
N2 - Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (SRCC1) 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 ≤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 IRCC1 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 XBCC1 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.
AB - Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (SRCC1) 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 ≤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 IRCC1 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 XBCC1 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.
UR - http://www.scopus.com/inward/record.url?scp=13444306156&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13444306156&partnerID=8YFLogxK
M3 - Article
C2 - 15705867
AN - SCOPUS:13444306156
SN - 0008-5472
VL - 65
SP - 722
EP - 726
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -