Promoter polymorphism of FASL confers protection against female-specific cancers and those of FAS impact the cancers divergently

We investigated risk association of FAS (−1377 G>A and −670 A>G) and FASL (−844 T>C) promoter polymorphisms with breast, ovarian, cervical, and endometrial cancers and report that the FASL −844 CC genotype was protective against breast, ovarian, cervical, and endometrial cancers ( P ≤ 0.01). On the other hand, FAS −1377 GA and AA variants increased risk of breast cancer. However, the GA variant of FAS −1377 was also found to be a risk factor for cervical cancer. In contrast, FAS −670 AG variant significantly lowered risk of breast cancer. Further, we also observed that risk association of co-occurrence of FAS and/or FASL variants with the cancers varied as compared to the presence of individual polymorphisms. Although risk and protective haplotypes of FAS SNPs were observed across the cancer phenotypes, the association of the haplotypes was significant for breast cancer alone with a 3-fold enhanced risk. The protective effect of the FASL CC genotype seen in this study suggests that similar biomolecular mechanisms involving FASL might play a role in female-specific cancers.