[Correlation of genetic polymorphisms in DNA repair genes ADPRT and XRCC1 to risk of gastric cancer].
OBJECTIVE
Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are 2 major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT 762Val-->Ala and XRCC1 399Arg-->Gln have been verified to associate with altered protein function and BER activity. This study was to examine the contribution of these 2 polymorphisms, alone or in combination, to the risk of developing gastric cancer.


METHODS
A total of 236 patients with gastric cancer and 708 cancer-free controls were genotyped for the 2 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model to evaluate the impact of these 2 polymorphisms on the risk of developing gastric cancer.


RESULTS
The subjects having the ADPRT Ala/Ala genotype had an OR of 2.07 (95% CI=1.33-3.21; P=0.001) compared with those having the Val/Val genotype. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the risk of gastric cancer in a super-multiplicative manner, with an OR of 5.32 (95% CI=1.12-28.57) for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, although the XRCC1 polymorphism itself was not associated with the risk of gastric cancer.


CONCLUSIONS
The ADPRT 762Val-->Ala polymorphism plays an important role in the development of gastric cancer, and the XRCC1 399Arg-->Gln polymorphism may serve as a risk modifier.
Zhang
Zhi
Z
Department of Oncologic Radiochemotherapy,Workers' Hospital of Tangshan City, Tangshan, Hebei 063000, P. R. China.
Miao
Xiao-Ping
XP
Tan
Wen
W
Guo
Yong-Li
YL
Zhang
Xue-Mei
XM
Lin
Dong-Xin
DX
D036002:ADP Ribose Transferases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013274:Stomach Neoplasms / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D036002:ADP Ribose Transferases