J Cell Mol Med 2009 Sep 27;13(9B):3699-702. Epub 2009 Feb 27.
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
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.