A common hereditary single-nucleotide polymorphism in the gene of FAS and colorectal cancer survival.
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.
Hofmann
Guenter
G
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. guenter.hofmann@medunigraz.at
Langsenlehner
Uwe
U
Langsenlehner
Tanja
T
Yazdani-Biuki
Babak
B
Clar
Heimo
H
Gerger
Armin
A
Fuerst
Florentine
F
Samonigg
Hellmut
H
Krippl
Peter
P
Renner
Wilfried
W
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012306:Risk; D019014:fas Receptor / Q000235:genetics*
D019014:fas Receptor