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...

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Bibliographic Details
Published in:Tumor biology 2015-04, Vol.36 (4), p.2709-2724
Main Authors: Nallapalle, Sateesh Reddy, Daripally, Sarika, Prasad, V. T. S Vidudala
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer Research
Cervical cancer
Endometrial cancer
Endometrial Neoplasms - genetics
Endometrial Neoplasms - pathology
Fas Ligand Protein - genetics
Female
Genetic Association Studies
Genetic Predisposition to Disease
Gynecology
Haplotypes
Humans
Middle Aged
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Polymorphism
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Research Article
Risk Factors
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
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Summary: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.
ISSN:1010-4283
1423-0380
DOI:10.1007/s13277-014-2896-7