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

2012; Elsevier BV; Volume: 73; Issue: 9 Linguagem: Inglês

10.1016/j.humimm.2012.06.001

1879-1166

Wijden Mahfoudh, Noureddine Bouaouina, Sallouha Gabbouj, Lotfi Chouchane,

Epigenetics and DNA Methylation

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 T1–T2 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.