title: Polymorphisms in mismatch repair genes are associated with risk and microsatellite instability of gastric cancer, and interact with life exposures.
abstract: BACKGROUND
  Epigenetic alterations of DNA mismatch repair (MMR) genes are associated with risk of gastric cancer (GC) by causing microsatellite instability (MSI). Less understood is the association of common polymorphisms in MMR genes with the risk and MSI phenotype of GC.
  
  
  METHODS
  A hospital-based study was conducted in China with 423 cases and 454 matched controls. Four potentially functional polymorphisms were selected and analyzed: rs1800734 in MLH1, rs2303428 in MSH2, rs735943 in EXO1, and rs11797 in TREX1.
  
  
  RESULTS
  The rs1800734 G-allele was associated with decreased risk of GC (GA or GG vs AA, OR=0.72; 95% CI: 0.50-1.05; Ptrend=0.029). For combined effects, a dose-response manner was observed in which GC risk was increased with increasing number of at-risk genotypes (Ptrend=0.039); this manner mainly existed in MSI GC (Ptrend=0.047) rather than in microsatellite stability GC, though neither single polymorphism was linked with MSI. For exposures, modified effects were observed from green tea drinking and soy foods intake on rs11797 (P for interaction=0.007 and 0.016, respectively).
  
  
  CONCLUSIONS
  The MLH1 rs1800734 polymorphism is associated with GC risk. Those at-risk genotypes have a joint effect on GC risk, which contributes to the MSI phenotype of GC. Life exposures modify GC risk, stratified by MMR genotypes.
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Li
authors.affiliation: Genetics and Molecular Biology Laboratory, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Hangang
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: yongqian_shu@sina.com.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.affiliation: The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: deqiang_wang@aliyun.com.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D045643:DNA Repair Enzymes / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: Gastric cancer; Microsatellite instability; Mismatch repair genes; Polymorphism