Polymorphisms and haplotypes in the Caspase 3, 7, and 8 genes and risk of endometrial cancer: a population-based, case-control study in a Chinese population
Caspase (CASP) 3, 7, and 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 CASP 3, 7, and 8 genes and risk of 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 (MIP) method. Of 35 selected SNPs, four in the CASP7 gene were in high linkage disequilibrium (rs11593766, rs3124740, rs11196445, and rs11196418) and associated with the risk of endometrial cancer. The AA genotype of rs11196418 (OR=0.36;95%CI:0.14–0.94) and the G allele of rs11593766 were associated with reduced risk (OR=0.75;95%CI=0.59–0.96 for carriers of one G allele; OR=0.70;95%CI=0.24–2.03 for carriers of two G alleles). The AA genotype of rs11196445 (OR=1.74;95%CI= 0.99–3.05), the CC genotype of rs3124740 (OR=1.36;95%CI= 1.06–1.75), and the GG genotype of rs10787498 in the CASP7 gene (OR=1.90;95%CI=1.16–3.11) were associated with increased risk compared with homozygotes of the major alleles. The gene-disease association appeared to be more pronounced among pre-menopausal women, although tests for multiplicative interaction between genes and menopausal status failed to reach statistical significance. The GG genotype of rs2705901 in the CASP3 gene was significantly associated with increased cancer risk compared with the CC genotype (OR=2.25;95%CI=1.03–4.95). No association was observed between polymorphisms of the CASP8 gene and risk of endometrial cancer. These findings suggest that genetic variants in CASP3 and CASP7 may play a role in endometrial cancer susceptibility.