Susceptibility to oral cancers with CD95 and CD95L promoter SNPs may vary with the site and gender

Abstract

We investigated risk association of oral cancers (tongue and buccal mucosa cancers) with FAS (-1377G > A and FAS -670 A > G) and FASL (-844 T > C) SNPs, in males and females. A case-control study of 535 oral cancer and 525 control subjects was performed. SNPs were detected in the genomic DNA isolated from peripheral blood using PCR-RFLP. We report FASL -844 T > C SNPs increased risk for buccal mucosa cancer in females but not in males. On the other hand, FAS genotypes did not alter the risk of the cancers in both females and males. However, co-occurrence of FAS -1377 GA and -670 GG, FAS -1377 AA and -670 GG genotypes, and combined genotypes of FAS and FASL (FAS -1377 AA + FAS -670 GG + FASL -844 CC) alter male susceptibility towards tongue cancer. In females, combined genotypes of FAS (-1377GA and -670 AA) were found to be a risk factor of buccal mucosa cancer (OR = 3.27, CI = 1.28-8.36; P ≤ 0.01). FASL variants (GA and AA) increased tongue cancer risk in females who were tobacco users compared to non-tobacco users. In conclusion, SNPs of the FAS and FASL might alter risk of tongue and buccal mucosa cancers differentially, in a gender-dependent manner.

Quantitative assessment of the relationship between Fas/FasL genes polymorphisms and head and neck cancer risk

“…In accordance with the eligibility criteria, 78 studies were excluded in the first step of duplicate screening, 164 studies were subsequently removed for title and abstract review, and 10 studies were removed because they were not case–control studies, molecular biology research, or without available data and not focused on specific loci. Eventually, 9 publications (20 independent case–control studies) involving 3179 patients and 4217 controls were selected, [ 24 , 32 – 39 ] including 7 case–control studies investigating Fas -670A>G, [ 24 , 32 , 34 , 35 , 37 – 39 ] 7 case–control studies investigating Fas -1377G>A, [ 32 , 33 , 35 – 39 ] and 6 case–control studies investigating FasL -844C>T, [ 32 , 35 – 39 ] respectively. Furthermore, 6 publications involved Asian populations, [ 34 – 39 ] and 3 studies involved Caucasian populations.…”

“…Eventually, 9 publications (20 independent case–control studies) involving 3179 patients and 4217 controls were selected, [ 24 , 32 – 39 ] including 7 case–control studies investigating Fas -670A>G, [ 24 , 32 , 34 , 35 , 37 – 39 ] 7 case–control studies investigating Fas -1377G>A, [ 32 , 33 , 35 – 39 ] and 6 case–control studies investigating FasL -844C>T, [ 32 , 35 – 39 ] respectively. Furthermore, 6 publications involved Asian populations, [ 34 – 39 ] and 3 studies involved Caucasian populations. [ 24 , 32 , 33 ] Regarding the HWE in controls, 1 case–control study deviated the HWE for the Fas -670A>G polymorphism [ 35 ] and Fas -1377G>A polymorphism, [ 37 ] and 2 case–control studies for the FasL -844C>T polymorphism.…”

“…[ 24 , 32 , 33 ] Regarding the HWE in controls, 1 case–control study deviated the HWE for the Fas -670A>G polymorphism [ 35 ] and Fas -1377G>A polymorphism, [ 37 ] and 2 case–control studies for the FasL -844C>T polymorphism. [ 36 , 39 ] The detailed characteristics of the included studies are summarized in Table 1 .…”

“…2 B for AG+GG vs AA model). Furthermore, sensitivity analysis indicated a slight risk of HNC when the study of Daripally et al [ 39 ] was omitted (Fig. 2 C for AG+GG vs AA model).…”

Molecular basis of sex differences in cancer: Perspective from Asia

“… 53 , 54 Genetic polymorphisms in FAS and FASL have been shown to confer variable cancer risks, potentially due to differences in the function of cytotoxic T cells and natural killer cells. 25 , 53 A case-control study in India studied the association of polymorphisms in CD95 (FAS/APO-1) and its ligand, CD95L (FASL), with oral cancers among males and females. 25 CD95 − CD95L is part of a receptor and death ligand system that mediates apoptosis which is important in the maintenance of immune cell homeostasis and immune elimination of cancer cells.…”