FASL−844 T/C polymorphism: A biomarker of good prognosis of breast cancer in the Tunisian population

Abstract

The single nucleotide polymorphism, rs763110 (-844 T/C) of the FASL gene, is located within a putative binding motif of CAAT/enhancer-binding protein β transcription factor. Higher basal expression of FASL is significantly associated with the FASL-844 C allele compared with the FASL-844 T allele suggesting that the FASL-844 T/C polymorphism may influence FASL expression and FASL-mediated signalling, and ultimately, the susceptibility to cancer. Therefore, we carried out a population-based study to estimate the FASL-844 C allele frequency in our population and to investigate, in a case-control study, the potential association of the FASL-844 T/C polymorphism with the risk and prognosis of breast cancer in Tunisia. FASL-844 T/C polymorphism was examined in a Tunisian population-based case-control of 438 patients with breast cancer and 332 control subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. By using TT genotype as reference, no significant association was found between any genotype and the risk of developing breast cancer. The frequency of the FASL-844 C allele was 46.3% among the cases and 43.7% among the controls. Similarly, by using T allele as reference, this difference was also not statistically significant. We observed FASL-844 CC genotype and FASL-844 C allele were significantly associated with SBR 1-2 tumour grade (OR=0.42, P=0.007; OR=0.65, P=0.005, respectively). In patients with diagnosis age ≤ 50 years, FASL-844 CC genotype and C allele showed significant associations with T(1)-T(2) clinical tumour size (OR=0.34, P=0.01; OR=0.65, P=0.02, respectively) and SBR grade 1-2 (OR=0.41, P=0.02; OR=0.62, P=0.01, respectively). A marginally significant association was also found with negative nodal status (OR=0.53, P=0.06; OR=0.73, P=0.07, respectively). Thus, the FASL-844 CC genotype and C allele seem to be associated with a good prognosis in patients with diagnosis age ≤ 50 years.