Polymorphisms and Haplotypes in the Caspase-3, Caspase-7, and Caspase-8 Genes and Risk for Endometrial Cancer: A Population-Based, Case-Control Study in a Chinese Population

Abstract

Caspase-3, caspase-7, and caspase-8 are important caspases in the apoptosis pathway and play an important role in the development and progression of cancer. We examined the association between genetic variants in the caspase-3, caspase-7, and caspase-8 genes and risk for endometrial cancer among Chinese women. Genotypes for 1,028 women with endometrial cancer and 1,003 healthy controls were determined with the Affymetrix MegAllele Targeted Genotyping System and Molecular Inversion Probe method. Of 35 selected single-nucleotide polymorphisms, four in the caspase-7 gene were in high linkage disequilibrium (rs11593766, rs3124740, rs11196445, and rs11196418) and associated with the risk for endometrial cancer. The AA genotype of rs11196418 [odds ratio, 0.36; 95% confidence interval (95% CI), 0.14-0.94] and the G allele of rs11593766 were associated with reduced risk (odds ratio of 0.75 and 95% CI of 0.59-0.96 for carriers of one G allele; odds ratio of 0.70 and 95% CI of 0.24-2.03 for carriers of two G alleles). The AA genotype of rs11196445 (odds ratio, 1.74; 95% CI, 0.99-3.05), the CC genotype of rs3124740 (odds ratio, 1.36; 95% CI, 1.06-1.75), and the GG genotype of rs10787498 in the caspase-7 gene (odds ratio, 1.90; 95% CI, 1.16-3.11) were associated with increased risk compared with homozygotes of the major alleles. The gene-disease association seemed to be more pronounced among premenopausal women, although tests for multiplicative interaction between genes and menopausal status failed to reach statistical significance. The GG genotype of rs2705901 in the caspase-3 gene was significantly associated with increased cancer risk compared with the CC genotype (odds ratio, 2.25; 95% CI, 1.03-4.95). No association was observed between polymorphisms of the caspase-8 gene and risk for endometrial cancer. These findings suggest that genetic variants in caspase-3 and caspase-7 may play a role in endometrial cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2009;18(7): 2114 -22)

Interactions between genetic polymorphisms in the apoptotic pathway and environmental factors on esophageal adenocarcinoma risk

“…A previous report has shown an inactivation mutation of CASP7 in esophageal cancer cells (34). Polymorphisms in CASP7 have been examined in several human cancers (35,36) but not in esophageal cancer until our recent report (11). In this study, we identified a significant interaction between CASP7 rs7907519 and smoking in EA cases.…”

Caspase Functions in Cell Death and Disease

“…Finally, a study of 1028 endometrial cancer patients and 1003 healthy controls examined potential links between caspase-3, -7, and -8 variant alleles and risk of endometrial cancer. Compared with the CC genotype, the GG genotype of rs2705901 in CASP3 was significantly associated with increased cancer risk (Xu et al 2009). Taken together, these results suggest that CASP3 polymorphisms and their haplotypes help to define an individual's genetic susceptibility to cancer development.…”

Old, new and emerging functions of caspases

“…151 Although somatic CASP3 mutations are rare in most tumors, 152 CASP3-variant alleles have been detected in squamous cell carcinomas of the head and neck (SCCHN) and associated with increased risk of SCCHN. 153 In addition, CASP3-variant alleles are associated with risk of endometrial cancer 154 and NHL 155 and multiple myeloma. 156 CASP3 polymorphisms in some lung cancer patients also show significantly decreased risk of disease.…”