Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

Pharmacogenetics and Genomics
Chunying LiQingyi Wei

Abstract

The FAS/FAS ligand (FASLG) system has a key role in regulating cell growth and thus tumorigenesis. Functional promoter polymorphisms of the FAS and FASLG genes alter the transcriptional activities, but no published study has investigated the role of these polymorphisms in the etiology of cutaneous malignant melanoma (CMM). In a hospital-based, case-control study of 602 non-Hispanic white CMM patients and 603 cancer-free age- and sex-matched control subjects, we genotyped FAS-1377G>A, FAS-670A>G, FASLG-844T>C and FASLG-IVS2nt-124G>A polymorphisms and assessed their respective associations with CMM risk. We found that an increased risk of CMM was associated with the FAS-1377GG [adjusted odds ratio (OR)=1.32; 95% confidence interval (CI)=1.00-1.75 for -1377GG] and -670AA (adjusted OR=1.28; 95% CI=1.00-1.65 for -670AA) genotypes compared to the -1377AA/AG and -670AG/GG genotypes, respectively; an increased risk of CMM was associated with the FASLG-IVS2nt-124AG+GG (OR=1.54; 95% CI=1.18-2.01) genotype compared to the AA genotype, but no evident risk was associated with any of the FAS-844T>C genotypes. In the combined analysis of these four variant alleles, we found that, compared to those having 0-3 variants, those having 4-8 variant...Continue Reading

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