Nonsynonymous polymorphisms in FAT4 gene are associated with the risk of esophageal cancer in an Eastern Chinese population

Int J Cancer. 2013 Jul 15;133(2):357-61. doi: 10.1002/ijc.28033. Epub 2013 Feb 12.

Abstract

FAT4 plays a crucial role in carcinogenesis as a key component of the Hippo signaling pathway. We hypothesized that potential functional polymorphisms in the FAT4 gene may modify the risk of esophageal cancer. To test this hypothesis, we evaluated the association between four nonsynonymous polymorphisms (rs1039808, rs12508222, rs1567047 and rs1014867) in FAT4 and esophageal cancer risk in a case-control study of 2,139 esophageal cancer cases and 2,273 controls in a Chinese population. We found that the T allele of rs1014867 (Pro4972Ser) was significantly associated with a decreased risk of esophageal cancer (odds ratio [OR]=0.77, 95% confidence interval [95% CI]=0.66-0.90; p=1.42 × 10(-3)). We also observed a borderline significant association between rs1039808 (Ala807Val) and esophageal cancer risk (OR=0.90, 95% CI=0.82-1.00; p=0.050), which was more prominent in non-drinkers (OR=0.82, 95% CI=0.71-0.94; p=6.53 × 10(-3)). Furthermore, we detected a significant interaction between rs1039808 genotypes and alcohol drinking on esophageal cancer risk (p=0.013). These findings indicate that the nonsynonymous variants rs1014867 (Pro4972Ser) and rs1039808 (Ala807Val) of FAT4 may contribute to esophageal cancer susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Cadherins / metabolism*
  • Case-Control Studies
  • China
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cadherins
  • FAT4 protein, human
  • Tumor Suppressor Proteins