RGD Reference Report - Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer. - Rat Genome Database

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Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer.

Authors: Miao, Xiaoping  Zhang, Xuemei  Zhang, Lingqiang  Guo, Yongli  Hao, Bingtao  Tan, Wen  He, Fuchu  Lin, Dongxin 
Citation: Miao X, etal., Gastroenterology. 2006 Aug;131(2):420-7. doi: 10.1053/j.gastro.2006.05.050.
RGD ID: 150530492
Pubmed: PMID:16890595   (View Abstract at PubMed)
DOI: DOI:10.1053/j.gastro.2006.05.050   (Journal Full-text)


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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XRCC1Humangastric cardia adenocarcinoma susceptibilityIAGP DNA:SNP:cds: p.R399Q (human)RGD 
Xrcc1Ratgastric cardia adenocarcinoma susceptibilityISOXRCC1 (Homo sapiens)DNA:SNP:cds: p.R399Q (human)RGD 
Xrcc1Mousegastric cardia adenocarcinoma susceptibilityISOXRCC1 (Homo sapiens)DNA:SNP:cds: p.R399Q (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XRCC1HumanGastric adenocarcinoma  IAGP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Xrcc1  (X-ray repair cross complementing 1)

Genes (Mus musculus)
Xrcc1  (X-ray repair complementing defective repair in Chinese hamster cells 1)

Genes (Homo sapiens)
XRCC1  (X-ray repair cross complementing 1)


Additional Information