Polymorphisms of the FAS and FASL genes and risk of breast cancer

Abstract

Abstract. FAS and its ligand FASL are crucial in apoptotic cell death. Loss of FAS and gain of aberrant FASL expression are common features of malignant transformation. This study was designed to investigate whether the functional polymorphisms of FAS -1377G/A (rs2234767) and FASL -844T/C (rs763110) affect the risk of developing breast cancer. Genotypes were analyzed by a polymerase chain reaction-restriction fragment length polymorphism assay in 436 breast cancer patients and 496 healthy controls. In this study, as compared to the wild-type homozygote and heterozygote, the distribution of the FAS -1377GG, GA and AA genotypes among breast cancer patients were significantly different from those among healthy controls (P=0.011), with the AA genotype being more prevalent among patients than the controls (P=0.003). Similarly, the frequencies of the FASL -844TT, TC and CC genotypes also significantly differed among breast cancer patients and healthy controls (P<0.001), with the CC genotype being significantly over-represented in breast cancer patients compared with the controls (P<0.001). In the unconditional logistic regression model following adjustment for age, the subjects carrying the FAS -1377AA genotype had a 1.75-fold increased risk [95% confidence interval (CI), 1.13-2.69] for development of breast cancer compared with patients carrying the GG genotype. Similarly, in the recessive model, the FASL -844CC genotype significantly increased the risk of breast cancer with an odds ratio (OR) of 1.92 (95% CI 1.46-2.54) compared with the TT or TT + TC genotypes. Our results suggest that functional polymorphisms in the death pathway genes FAS and FASL significantly contribute to the occurrence of breast cancer.

Effects of FasL Expression in Oral Squamous Cell Cancer

“…Accordingly,they become more sensitive to apoptosis when they interact with cells that express the FasL on their surface (Nagata et al, 1995;Ehrenschwender et al, 2009). Evidence for this mechanism of tumor immune privilege has been provided for several cancers (Zhou et al, 2006;Wu et al, 2010;Gomes et al, 2011;Cai et al, 2012;Tian et al, 2012;Wang et al, 2012) that have been shown to express FasL, including skin, lung, breast, and cervical cancers, gastric cancer. To date, the molecular events underlying the role of Fas/FasL in the progression to oral carcinoma are poorly understood (Chen et al, 1999).…”

Single nucleotide polymorphisms of the Fas gene are associated with papillary thyroid cancer

“…FasL polymorphism was associated with the increased risk of neuroblastoma [21], laryngeal and hypopharyngeal squamous cell cancer [23], epithelial ovarian cancer [24], breast cancer [26], and gastric cardiac adenocarcinoma [46]. Also FasL polymorphism was a low risk factor for oral cancer [25], pancreatic cancer [30], and breast cancer [19,32].…”

“…Recently, SNPs of the Fas or FasL genes have been shown to be associated with an increased risk of several cancers [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and with the prognosis of several cancers [34][35][36][37][38][39][40]. However, the association between thyroid cancer and SNPs of the Fas and FasL genes is not clear.…”

Increased Resistance to Staphylococcus aureus Endophthalmitis in BALB/c Mice: Fas Ligand Is Required for Resolution of Inflammation but Not for Bacterial Clearance

“…The mFasL.2 allotype exhibits 9-fold-higher binding affinity to the Fas receptor and cytotoxic activity against Fas ϩ target cells than mFasL.1. Polymorphisms in the FasL gene have also been found in humans and have been associated with increased risk of some cancers (18)(19)(20). However, it is not known how these FasL polymorphisms may influence the immune response and susceptibility to infection in humans.…”