TY - JOUR
T1 - Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma
AU - Li, Chunying
AU - Larson, Derek
AU - Zhang, Zhengdong
AU - Liu, Zhensheng
AU - Strom, Sara S.
AU - Gershenwald, Jeffrey E.
AU - Prieto, Victor G.
AU - Lee, Jeffrey E.
AU - Ross, Merrick I.
AU - Mansfield, Paul F.
AU - Cormier, Janice N.
AU - Duvic, Madeleine
AU - Grimm, Elizabeth A.
AU - Wei, Qingyi
PY - 2006/4
Y1 - 2006/4
N2 - 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 alleles had a significantly increased risk for CMM (OR = 1.38; 95% CI = 1.10-1.73), and this risk was more pronounced in subgroups of old (> 50 years) males, and those who were at low risk of sunlight-induced CMM, except for having fair skin colour, moles, dysplastic nevi and a family history of cancer. In conclusion, genetic variants in the FAS and FASLG genes may contribute to the etiology of CMM in the general population, particularly in those with a low risk of sunlight-induced CMM.
AB - 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 alleles had a significantly increased risk for CMM (OR = 1.38; 95% CI = 1.10-1.73), and this risk was more pronounced in subgroups of old (> 50 years) males, and those who were at low risk of sunlight-induced CMM, except for having fair skin colour, moles, dysplastic nevi and a family history of cancer. In conclusion, genetic variants in the FAS and FASLG genes may contribute to the etiology of CMM in the general population, particularly in those with a low risk of sunlight-induced CMM.
KW - Cell cycle
KW - Death pathway
KW - Genetic susceptibility
KW - Molecular epidemiology
KW - Skin cancer
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U2 - 10.1097/01.fpc.0000199501.54466.de
DO - 10.1097/01.fpc.0000199501.54466.de
M3 - Article
C2 - 16538172
AN - SCOPUS:33645074700
SN - 1744-6872
VL - 16
SP - 253
EP - 263
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
IS - 4
ER -