title: Genetic variations in the SMAD4 gene and gastric cancer susceptibility.
abstract: OBJECTIVE
  To explore the association between mothers against decapentaplegic homolog 4 (SMAD4) gene polymorphisms and gastric cancer risk.
  
  
  METHODS
  Five tagging single nucleotide polymorphisms (tSNPs) in the SMAD4 gene were selected and genotyped in 322 gastric cancer cases and 351 cancer-free controls in a Chinese population by using the polymerase chain reaction restriction fragment length polymorphism method. Immunohistochemistry was used to examine SMAD4 protein expression in 10 normal gastric tissues adjacent to tumors.
  
  
  RESULTS
  In the single-locus analysis, two significantly decreased risk polymorphisms for gastric cancer were observed: the SNP3 rs17663887 TC genotype (adjusted odds ratio = 0.38, 95% confidence interval: 0.21-0.71), compared with the wild-type TT genotype and the SNP5 rs12456284 GG genotype (0.31, 0.16-0.60), and with the wild-type AA genotype. In the combined analyses of these two tSNPs, the combined genotypes with 2-3 protective alleles (SNP3 C and SNP5 G allele) had a significantly decreased risk of gastric cancer (0.28, 0.16-0.49) than those with 0-1 protective allele. Furthermore, individuals with 0-1 protective allele had significantly decreased SMAD4 protein expression levels in the normal tissues adjacent to tumors than those with 2-3 protective alleles (P = 0.025).
  
  
  CONCLUSIONS
  These results suggest that genetic variants in the SMAD4 gene play a protective role in gastric cancer in a Chinese population.
authors.affiliation: Department of Molecular and Genetic Toxicology, School of Public Health, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu Province, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wu
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zhu
authors.forename: Qing-Hong
authors.initials: QH
authors.lastname: Zhao
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Zhang
authors.forename: Shi-Zhi
authors.initials: SZ
authors.lastname: Wang
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Wang
authors.forename: Wei-Da
authors.initials: WD
authors.lastname: Gong
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Zheng-Dong
authors.initials: ZD
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D051901:Smad4 Protein / Q000032:analysis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000235:genetics*
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein