Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Université de Monastir, 5019 Monastir, Tunisia.
Hum Immunol. 2012 Sep;73(9):932-8. doi: 10.1016/j.humimm.2012.06.001. Epub 2012 Jun 22.
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.
FASL 基因的单核苷酸多态性 rs763110(-844T/C)位于 CAAT/增强子结合蛋白β转录因子的假定结合基序内。与 FASL-844T 等位基因相比，FASL 的基础表达较高与 FASL-844C 等位基因显著相关，这表明 FASL-844T/C 多态性可能影响 FASL 的表达和 FASL 介导的信号转导，并最终影响癌症的易感性。因此，我们进行了一项基于人群的研究，以估计我们人群中 FASL-844C 等位基因的频率，并在突尼斯的病例对照研究中研究 FASL-844T/C 多态性与乳腺癌风险和预后的潜在关联。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析，在一个基于人群的突尼斯病例对照研究中，对 438 名乳腺癌患者和 332 名对照进行了 FASL-844T/C 多态性检测。以 TT 基因型为参考，未发现任何基因型与患乳腺癌的风险之间存在显著关联。FASL-844C 等位基因在病例中的频率为 46.3%，在对照中的频率为 43.7%。同样，以 T 等位基因为参考，这种差异也无统计学意义。我们观察到 FASL-844CC 基因型和 FASL-844C 等位基因与 SBR1-2 肿瘤分级显著相关（OR=0.42，P=0.007；OR=0.65，P=0.005）。在诊断年龄≤50 岁的患者中，FASL-844CC 基因型和 C 等位基因与 T1-T2 临床肿瘤大小显著相关（OR=0.34，P=0.01；OR=0.65，P=0.02）和 SBR 分级 1-2（OR=0.41，P=0.02；OR=0.62，P=0.01）。与阴性淋巴结状态也存在边缘显著关联（OR=0.53，P=0.06；OR=0.73，P=0.07）。因此，FASL-844CC 基因型和 C 等位基因似乎与诊断年龄≤50 岁的患者的良好预后相关。
