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

作者：Hofmann Guenter^*; Langsenlehner Uwe; Langsenlehner Tanja; Yazdani Biuki Babak; Clar Heimo; Gerger Armin; Fuerst Florentine; Samonigg Hellmut; Krippl Peter; Renner Wilfried

来源：Journal of Cellular and Molecular Medicine, 2009, 13(9B): 3699-3702.

DOI：10.1111/j.1582-4934.2009.00720.x

• FAS
• apoptosis
• colorectal cancer
• survival
• polymorphism

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.

• 出版日期2009-9
• 单位河北医科大学