Abstract | BACKGROUND & AIMS:
Adenosine diphosphate ribosyl transferase ( ADPRT) and x-ray repair cross-complementing 1 (XRCC1) are major DNA base excision repair proteins acting interactively in repair processes. This study examined the effects of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1 interaction in vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA) risk. METHODS: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and XRCC1 variant complementary DNA ( cDNA) constructs were examined by immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500 patients and 1000 controls, and odds ratios ( ORs) were estimated by logistic regression. RESULTS: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1-399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95% CI, 1.55-3.04) and 1.61 (95% CI, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC1 Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1 Gln/Gln genotypes, 6.43; 95% CI, 1.80-22.97). A supermultiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CIs) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or = 24 or > 24 pack-years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively (Ptrend test = .008). CONCLUSIONS: The ADPRT and XRCC1 polymorphisms confer host susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction and attenuated base excision repair capacity.
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Authors | Xiaoping Miao, Xuemei Zhang, Lingqiang Zhang, Yongli Guo, Bingtao Hao, Wen Tan, Fuchu He, Dongxin Lin |
Journal | Gastroenterology
(Gastroenterology)
Vol. 131
Issue 2
Pg. 420-7
(Aug 2006)
ISSN: 0016-5085 [Print] United States |
PMID | 16890595
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Neoplasm
- DNA-Binding Proteins
- X-ray Repair Cross Complementing Protein 1
- XRCC1 protein, human
- ADP Ribose Transferases
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Topics |
- ADP Ribose Transferases
(genetics)
- Adult
- Cardia
(pathology)
- DNA, Neoplasm
(genetics)
- DNA-Binding Proteins
(genetics)
- Female
- Follow-Up Studies
- Genetic Predisposition to Disease
- Genotype
- Humans
- Male
- Middle Aged
- Polymorphism, Genetic
- Prognosis
- Retrospective Studies
- Risk Factors
- Smoking
(adverse effects, genetics)
- Stomach Neoplasms
(genetics, metabolism, pathology)
- X-ray Repair Cross Complementing Protein 1
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