FAS and FAS Ligand Polymorphisms in the Promoter Regions and Risk of Gastric Cancer in Southern China

Abstract

The FAS and FAS ligand (FASLG) system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumorigenesis. Functional promoter polymorphisms of the FAS and FASLG genes can alter transcriptional activities and thus alter risk of cancer. We hypothesized that the FAS -1377G>A, FAS -670A>G, and FASLG -844T>C polymorphisms in the promoter regions are associated with risk of gastric cancer. In a population-based case-control study of 332 gastric cancer cases and 324 controls, we genotyped these three polymorphisms and evaluated their association with risk of gastric cancer. We found that the FAS and FASL genotypes and the FAS haplotypes had no significant associations with risk of gastric cancer. In addition, there was no significant interaction between the FAS and FASL polymorphisms in the development of gastric cancer. The FAS and FASLG polymorphisms may not contribute to risk of gastric cancer in the southern Chinese population.

The Relationship of Fas Promoter Polymorphisms and Breast Cancer Risk in North-West of Iran: A Haplotype and in Silico Analysis

“…Studies on childhood acute lymphoblastic leukemia (15) and hepatitis B virus infection (29) in Iran have shown no significant association in fas-1377G > A and fas-670A > G with the risk of both diseases that were in agreement with the findings of this study. Some of the studies have demonstrated that the A allele has a higher frequency among cases than healthy subjects, (5,12); however, contrastingly in some others, the A allele had a higher frequency in controls in comparison with patients (8,16,30). In the present study, the frequency of fas-1377A allele and GA genotype was higher in patients rather than the control group, but the differences were not significant.…”

“…Abnormal regulation of apoptotic pathways and consequent deregulation of mentioned biological processes lead to the development of human malignancies (3). Death receptor on the surface of many cell types, fas and its ligand, fasL as members of the tumor necrosis factor superfamily (TNF), interact to initiate the extrinsic death signal pathway, which consequently leads to apoptotic cell death (7,(9)(10)(11)(12). Structural alterations of fas and fasL may influence the expression of them and consequently result in the development of various tumors, such as breast tumors (7,13).…”

“…Structural alterations of fas and fasL may influence the expression of them and consequently result in the development of various tumors, such as breast tumors (7,13). The human fas on 10q24.1 (12,14), which consists of 9 exons and 8 introns, (14) has 2 single nucleotide polymorphisms (SNPs) in its promoter. One of them is a G-A transition at nucleotide number -1377 (fas-1377G > A) in the silencer region, and the other is an A-G transition at nucleotide number -670 (fas-670A > G) in the enhancer site.…”

Association Between the FAS/FASL Polymorphisms and Gastric Cancer Risk: A Meta-Analysis

“…Asian Pacific Journal of Cancer Prevention, Vol 13, 2012 947 DOI:http://dx.doi.org/10.7314/APJCP.2012.13.3 five studies for FAS -670A>G polymorphism, met the inclusion criteria (Ikehara et al, 2006;Hsu et al, 2008;Wang et al, 2009;Zhou et al, 2010;Kupcinskas et al, 2011;Liu et al, 2011;Zhang et al, 2011). The characteristics of each article are listed in Table 1.…”

“…Over the last two decades, numerous case-control studies have been performed to clarify the relationship between FAS/FASL polymorphisms and GC risk in human (Ikehara et al, 2006;Hsu et al, 2008;Wang et al, 2009;Zhou et al, 2010;Liu et al, 2011;Kupcinskas et al, 2011;Zhang et al, 2011). The most extensively studied polymorphisms are the G to A substitution at position -1377 (-1377G>A, rs2234767) and A to G substitution at position -670 (-670A>G, rs1800682), and the C to T substitution at position -844 (-844C>T, rs763110) in the promoter region of FAS/FASL gene.…”