title: Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
authors.forename: Bingtao
authors.initials: B
authors.lastname: Hao
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics*; D000328:Adult; D002299:Cardia / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D036002:ADP Ribose Transferases