A literature-based systematic HuGE review and meta-analysis show that CASP gene family polymorphisms are associated with risk of lung cancer

The caspase (CASP) gene family is known to be involved in apoptosis, cytokine maturation, cell growth, and differentiation. A large number of single nucleotide polymorphisms (SNPs) in the CASP gene family have been increasingly recognized as important regulators in the development of lung cancer. However, this specific association is still controversial. In this Human Genome Epidemiology review and meta-analysis, we summarized the available evidence associating lung cancer with the CASP gene family. Seven studies, which included 1155 lung cancer cases and 1120 healthy controls, met the inclusion criteria and were included in our meta-analysis. In seven studies, 19 different SNPs have been studied in seven CASP genes, including CASP-1, -2, -5, -7, -8, -9, and -10. Meta-analysis results showed positive associations between heterozygote (A/G) of rs507879 in the CASP-5 gene, the T allele of rs12415607 in the CASP-7 gene, and the T allele and T carrier (C/T+T/T) of rs4645981 in the CASP-9 gene with lung cancer susceptibility [odds ratio (OR) = 1.83, 95% confidence interval (95% CI) = 1.07-3.12, P = 0.03; OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.43, 95%CI = 1.12-1.81, P = 0.004; OR = 1.46, 95%CI = 1.10-1.93, P = 0.009; respectively]. However, we found that homozygote (G/G) of rs2227310 in the CASP-7 gene, del allele, heterozygote (ins/del), and del carrier (ins/del + del/del) of rs3834129 in CASP-8 could be protective factors for lung cancer (OR = 0.17, 95%CI = 0.14-0.21, P = 0.0003; OR = 0.83, 95%CI = 0.72-0.97, P = 0.02; OR = 0.74, 95%CI = 0.64-0.85, P < 0.0001; OR = 0.81, 95%CI = 0.71-0.93, P = 0.002; respectively). In conclusion, based on this meta-analysis, we suggest that SNPs in CASP-5, -7, -8, and -9 are associated with susceptibility to lung cancer.