- 作者：C. Li ; J. Lu ; Z. Hu ; Z. Liu ; L.E. Wang ; E.M. Sturgis ; A.K. El-Naggar ; V.G. Prieto ; J.E. Gershenwald ; J.E. Lee ; E.A. Grimm ; Q. Wei
- 刊名：Annals of Epidemiology
- 出版年：2007
- 出版时间：September 2007
- 年：2007
- 卷：17
- 期：9
- 页码：753
- 全文大小：29 K
Purpose
Caspase 8 is an apoptosis-related cysteine peptidase that is mainly involved in the death receptor (FAS/FASLG) pathway. Studies have shown that the CASP8 D302H minor variant genotypes protect against breast cancer risk in different ethnic groups and that the minor functional -652 6N del allele protected against several types of cancer in a Chinese population. This study was to identify such an association in Caucasians.Methods
We conducted a hospital-based case-control study of 805 cutaneous melanoma and 1023 squamous cell carcinoma of the head and neck (SCCHN) and 1584 cancer-free controls to assess the association between two selected genetic polymorphisms (-652 6N ins/del and D302H) of the CASP8 gene and risk of melanoma and SCCHN. We genotyped these two polymorphisms by the PCR-based assays and estimated related haplotypes for all subjects and detected camptothecin-induced apoptotic cells in cultured lymphocytes from 170 cancer-free controls. We used multivariate unconditional logistic regression analysis to calculate the odds ratios and their 95 % confidence intervals and assessed gene-environment interactions.
Results
We found that the CASP8 -652 6N del variant genotypes or haplotypes carrying the -652 6N del allele protected against risk of both melanoma (adjusted OR = 0.74, 95 % CI = 0.58 to 0.95) and SCCHN (adjusted OR = 0.73, 95 % CI = 0.57 to 0.95), whereas CASP8 302H variant genotypes protected against risk of melanoma (adjusted OR = 0.70, 95 % CI = 0.57 to 0.85) but not SCCHN (adjusted OR = 1.06, 95 % CI = 0.87 to 1.30), compared to the common homozygous genotypes. We also found that the number of the CASP8 -652 6N del (but not 302H) variant tended to be correlated with increased levels of camptothecin-induced apoptosis.
Conclusion
The CASP8 -652 6N del variant is risk factor for the studies cancers in Caucasians and may have an effect on apoptosis in response to DNA damage through the mitochondrial pathway, in addition to the FAS/FASLG-mediated pathway. Further validation by population-based case-control studies and mechanistic studies are warranted.