CASP-9 gene functional polymorphisms and cancer risk: a large-scale association study plus meta-analysis.

We investigated the association between CASP-9 polymorphisms and susceptibility to neoplasm. Fourteen studies with a total of 2733 neoplasm cases and 3352 healthy controls were included. Meta-analysis showed that the rs4645981 T allele and the rs4645981 T allele carrier were positively associated with neoplasm susceptibility [odds ratio (OR) = 1.43, 95% confidence interval (95%CI) = 1.12-1.81, P = 0.004; OR = 1.46, 95%CI = 1.10-1.93, P = 0.009, respectively]. However, the rs1052576 A allele, rs1052576 A carrier, rs2308941 T allele, and rs2308941 T carrier might decrease the risk of cancer (OR = 0.72, 95%CI = 0.58-0.89, P = 0.003; OR = 0.76, 95%CI = 0.63-0.92, P = 0.004; OR = 0.20, 95%CI = 0.09-0.45, P < 0.0001; OR = 0.21, 95%CI = 0.06-0.75, P = 0.02, respectively). There was no significant association between rs1263, rs1052571, rs2308950, rs4645978, rs4645980, rs4645982, and rs4646018 and cancer risk (all P > 0.05). In conclusion, this meta-analysis suggests that CASP-9 gene polymorphisms are involved in the pathogenesis of various cancers. The rs4645981 T allele and the rs4645981 T allele carrier might increase the risk of cancer, but the rs1052576 A allele, rs1052576 A carrier, rs2308941 T allele, and rs2308941 T carrier might be protective.

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.

Meta-analysis demonstrates association of XRCC1 genetic polymorphism Arg399Gln with esophageal cancer risk in the Chinese population.

We made a meta-analysis of the association between X-ray cross-complementing gene 1 (XRCC1) genetic polymorphism Arg399Gln and esophageal cancer (EC) risk. Statistical analysis was performed with the Review Manager version 4.2.8 software program and STATA version 11.0. We selected 16 case-control studies for this meta-analysis, including 3591 EC cases and 5752 controls. Overall, the Gln399 allele was not associated with EC risk, compared with the Arg399 allele in the populations included in the analysis. However, stratified analysis revealed that the Gln399 allele was associated with increased EC risk among the Chinese population in a recessive model [odds ratio (OR) = 1.42; 95% confidence interval (95%CI) = 1.07-1.90; P = 0.02 for heterogeneity] and by homozygote contrast (OR = 1.43; 95%CI = 1.05-1.96; P = 0.02 for heterogeneity), particularly for the tumor histology of squamous cell carcinoma (OR = 1.46; 95%CI = 1.10-1.95 for the recessive model and OR = 1.42; 95%CI = 1.03-1.95 for the homozygote contrast). We conclude that the XRCC1 Arg399Gln polymorphism has potential as a biomarker for EC susceptibility in the Chinese population, particularly for squamous cell carcinoma.