Communicated by Stephen Chanock
Article first published online: 18 JUN 2008
© 2008 Wiley-Liss, Inc.
Volume 29, Issue 12, pages 1443–1451, December 2008
How to Cite
Li, C., Zhao, H., Hu, Z., Liu, Z., Wang, L.-E., Gershenwald, J. E., Prieto, V. G., Lee, J. E., Duvic, M., Grimm, E. A. and Wei, Q. (2008), Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma. Hum. Mutat., 29: 1443–1451. doi: 10.1002/humu.20803
Current address for Chunying Li: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
- Issue published online: 21 NOV 2008
- Article first published online: 18 JUN 2008
- Manuscript Accepted: 20 MAR 2008
- Manuscript Received: 30 NOV 2007
- National Institutes of Health (NIH)
- National Cancer Institute (NCI). Grant Numbers: R01 CA100264, P50 CA093459
- National Institute of Environmental Health Sciences (NIEHS). Grant Number: ES11740
- death pathway;
- genetic susceptibility;
- molecular epidemiology;
- skin cancer;
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.