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Genetic variants and haplotypes of the caspase‐8 and caspase‐10 genes contribute to susceptibility to cutaneous melanoma

Genetic variants and haplotypes of the caspase‐8 and caspase‐10 genes contribute to... Caspase‐8 (CASP8) and caspase‐10 (CASP10) play key roles in regulating apoptosis, and their functional polymorphisms may alter apoptosis and cancer risk. However, no reported studies have investigated the association between such polymorphisms and the risk of cutaneous melanoma (CM). In a hospital‐based study of 805 non‐Hispanic white patients with CM and 835 cancer‐free age‐, sex‐, and ethnicity‐matched controls, we genotyped three reported putatively functional polymorphisms of CASP8 and CASP10—CASP8 D302 H (rs1045485:G>C), CASP8 –652 6N del (rs3834129:–/CTTACT), and CASP10 I522L (rs13006529:A>T)—and assessed their associations with risk of CM and interactions with known risk factors for CM. We also calculated the false‐positive report probability (FPRP) for significant findings. CASP8 302 H variant genotypes (DH: adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.50–0.98; DH+HH: unadjusted OR, 0.78; 95% CI, 0.62–0.98; FPRP, 0.79) and CASP8 –652 6N del variant genotypes (ins/del: OR, 0.74; 95% CI, 0.57–0.97; ins/del+del/del: OR, 0.76; 95% CI, 0.61–0.95; FPRP, 0.61) were associated with significantly lower CM risk than were the DD and ins/ins genotypes, respectively. However, the CASP10 522L variant genotypes were not associated with significantly altered CM risk. Also, the D‐del‐I haplotype was associated with a significantly lower CM risk (OR, 0.52; 95% CI, 0.37–0.74; FPRP, 0.04) than was the most common haplotype, D‐ins‐I. Furthermore, multivariate logistic regression analysis revealed that CASP8 D302 H, CASP8 –652 6N del, and CASP10 I522L were independent risk factors for CM. Therefore, these CASP8 and CASP10 polymorphisms may be biomarkers for susceptibility to CM. Hum Mutat 0, 1–9, 2008. © 2008 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Mutation Wiley

Genetic variants and haplotypes of the caspase‐8 and caspase‐10 genes contribute to susceptibility to cutaneous melanoma

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References (48)

Publisher
Wiley
Copyright
Copyright © 2008 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1059-7794
eISSN
1098-1004
DOI
10.1002/humu.20803
pmid
18563783
Publisher site
See Article on Publisher Site

Abstract

Caspase‐8 (CASP8) and caspase‐10 (CASP10) play key roles in regulating apoptosis, and their functional polymorphisms may alter apoptosis and cancer risk. However, no reported studies have investigated the association between such polymorphisms and the risk of cutaneous melanoma (CM). In a hospital‐based study of 805 non‐Hispanic white patients with CM and 835 cancer‐free age‐, sex‐, and ethnicity‐matched controls, we genotyped three reported putatively functional polymorphisms of CASP8 and CASP10—CASP8 D302 H (rs1045485:G>C), CASP8 –652 6N del (rs3834129:–/CTTACT), and CASP10 I522L (rs13006529:A>T)—and assessed their associations with risk of CM and interactions with known risk factors for CM. We also calculated the false‐positive report probability (FPRP) for significant findings. CASP8 302 H variant genotypes (DH: adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.50–0.98; DH+HH: unadjusted OR, 0.78; 95% CI, 0.62–0.98; FPRP, 0.79) and CASP8 –652 6N del variant genotypes (ins/del: OR, 0.74; 95% CI, 0.57–0.97; ins/del+del/del: OR, 0.76; 95% CI, 0.61–0.95; FPRP, 0.61) were associated with significantly lower CM risk than were the DD and ins/ins genotypes, respectively. However, the CASP10 522L variant genotypes were not associated with significantly altered CM risk. Also, the D‐del‐I haplotype was associated with a significantly lower CM risk (OR, 0.52; 95% CI, 0.37–0.74; FPRP, 0.04) than was the most common haplotype, D‐ins‐I. Furthermore, multivariate logistic regression analysis revealed that CASP8 D302 H, CASP8 –652 6N del, and CASP10 I522L were independent risk factors for CM. Therefore, these CASP8 and CASP10 polymorphisms may be biomarkers for susceptibility to CM. Hum Mutat 0, 1–9, 2008. © 2008 Wiley‐Liss, Inc.

Journal

Human MutationWiley

Published: Dec 1, 2008

Keywords: apoptosis; death pathway; genetic susceptibility; molecular epidemiology; skin cancer; CASP8; CASP10

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