A common hereditary single-nucleotide polymorphism in the gene of FAS and colorectal cancer survival

J Cell Mol Med. 2009 Sep;13(9B):3699-702. doi: 10.1111/j.1582-4934.2009.00720.x. Epub 2009 Feb 27.

Abstract

Apoptosis plays an important role in embryogenesis, autoimmunity and tumourigenesis. Cell surface death receptors such as TNFRSF6 (FAS) confer a major apoptotic effect. A single-nucleotide polymorphism in the FAS promoter gene, -670A/G, modulates apoptotic signalling and has been related to susceptibility and progression of a variety of cancers. The present study aimed to evaluate the role of this polymorphism for survival of patients with colorectal cancer. We performed a retrospective analysis including 433 patients with histologically confirmed colorectal cancer. A Cox regression model including FAS -670 genotypes, age at diagnosis, tumour grading, primary tumour size, number of lymph nodes examined, number of metastatic lymph nodes, tumour stage and application of fluorouracil-based adjuvant chemotherapy was used to estimate the effect of the FAS genotype on survival. FAS -670A/G genotype frequencies were 24.2% (AA), 46.3% (AG) and 29.5% (GG). Forty-nine patients were excluded from the Cox regression analysis because of missing values. Out of the remaining 384 patients, 69 (18%) died during a follow-up of maximum 10 years. Mean follow-up time was 58 +/- 34 months (median 55 months). Carriers of the homozygous FAS -670GG genotype had a significantly lower survival rate compared with AA/AG genotype carriers (relative risk 1.76, 95% confidence interval 1.08-2.87; P= 0.023). The FAS -670A/G polymorphism may be associated with overall survival time of patients with colorectal cancer.

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Regression Analysis
  • Retrospective Studies
  • Risk
  • fas Receptor / genetics*

Substances

  • fas Receptor