HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk

Abstract

ABSTRACT. Genetic variations in the caspase genes CASP-3 and CASP-7 are known to be involved in apoptosis, cytokine maturation, cell growth and differentiation. Polymorphisms of CASP-3 and CASP-7 genes have been increasingly recognized as important regulators in the development of cancer. However, whether there is a specific association is still controversial. Therefore, we made a Human Genome Epidemiology review and meta-analysis to explore the association between polymorphisms of CASP-3 and CASP-7 genes and cancer risk. Based on the inclusion criteria, we examined 9 case-control studies, with a total of 3142 cancer cases and 3670 healthy controls. Meta-analysis results showed that the homozygote (CC) of rs2705897 in the CASP-3 gene is positively associated with cancer susceptibility [odds ratio (OR) = 4.36, 95% confidence interval (CI) = 1.26-15.11, P = 0.02], while the C allele and C carrier (TC+CC) of rs1049216 are negatively associated with cancer risk (OR = 0.81, 95%CI = 0.69-0.95, P = 0.01; OR = 0.78, 95%CI= 0.63-0.97, P = 0.02, respectively). The G allele and G carrier of rs4647603 (A/G) in CASP-3 had positive associations with cancer susceptibility (OR = 1.69, 95%CI = 1.37-2.09, P < 0.001; OR = 1.93, 95%CI = 1.26-2.93, P = 0.002, respectively). The T allele of rs12415607, the G allele and homozygote (GG) of rs2227310, and homozygote (CC) of rs3124740 also had positive associations with cancer risk (OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.17, 95%CI = 1.01-1.34, P = 0.03; OR = 1.34, 95%CI = 1.04-1.74, P = 0.03; OR = 1.30, 95%CI = 1.04-1.63, P = 0.02, respectively). In addition, homozygote (AA) of rs11196418 showed a significant negative association with cancer risk (OR = 0.36, 95%CI = 0.14-0.93, P = 0.03). These meta-analysis results demonstrated that CASP-3 and CASP-7 genetic polymorphisms are involved in the pathogenesis of cancer.

Associations of genetic variation in CASP3 gene with noise-induced hearing loss in a Chinese population: a case–control study

“…By calculating the numbers of the high-risk genotype, we found that the risk of NIHL in those carrying two risk genotypes was 1.787-fold higher than in those carrying no risk genotype (OR = 1.787, 95%CI = 1.104–2.892). This is similar to the results of Yan et al [20]. By the stratified analysis, positive results were only founded when noise intensity was <85 dB(A) or CNE < 90 dB(A), and the effects of high-risk genotype were not observed when noise intensity was ≥85 dB(A) or CNE ≥90 dB(A).…”

Caspase polymorphisms and prognosis of hepatocellular carcinoma

“…As an effector CASP, CASP3 plays an important role in the execution phase of apoptosis, also in the development and progression of cancers [16–17]. Several previous studies have shown associations of CASP3 polymorphisms on the risk of different types of cancer, including HCC [13, 18–20]. Moreover, studies in several tumor types indicated that the expression levels of CASP3 have effects on the development and survival of cancers [8, 17, 21].…”

Old, new and emerging functions of caspases

“…Recently, Human Genome Epidemiology review and meta-analysis polymorphisms of CASP3 and CASP7 genes were found to be linked to cancer risk. 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.…”