A Meta-Analysis of Caspase 9 Polymorphisms in Promoter and Exon Sequence on Cancer Susceptibility

Abstract

BackgroundCaspases are important regulators and executioners in apoptosis pathway and have been defined as either tumor suppressors or oncogenes. Polymorphisms in promoter and exon of caspase 9 were shown to confer genetic susceptibility to multiple cancers, but the results were inconsistent. To accomplish a more precise estimation of the relationship, a meta-analysis was performed.Methodology/Principal FindingsWe assessed published studies of the association between caspase 9 polymorphisms and cancer risk from nine studies with 5,528 subjects for rs4645978, six studies with 2,403 subjects for rs105276 and two studies for rs4645981. Overall meta-analysis indicated that no evidence of an association between rs4645978 and cancers was found. Through the stratified analysis, statistically significant reduced cancer risks were observed among Caucasians (AG vs AA: OR = 0.81, 95% CI = 0.66–0.99, P heterogeneity = 0.150 and the dominant model: OR = 0.86, 95% CI = 0.75–0.99, P heterogeneity = 0.290) and prostate cancer. As for rs105276, Ex5+32G>A polymorphism was found with protective effect in overall meta-analysis (AA vs GG: OR = 0.75, 95% CI = 0.60–0.92, P heterogeneity = 0.887; A vs G: OR = 0.85, 95% CI = 0.77–0.95, P heterogeneity = 0.739 and the recessive model: OR = 0.68, 95% CI = 0.56–0.82, P heterogeneity = 0.309) and Asians group. While for rs4645981, a statistically significant increase in risk of lung cancer was shown in Asians (T vs C: OR = 1.23, 95% CI = 1.07–1.42, P heterogeneity = 0.399 and the dominant model: OR = 1.22, 95% CI = 1.04–1.43, P heterogeneity = 0.660).Conclusions/SignificanceOur meta-analysis suggests that the caspase 9 rs4645978 most likely contributes to decreased susceptibility to cancer in Caucasians and prostate cancer. The A allele of rs105276 might be a protective factor for cancer, especially for Asians. However, it seems that rs4645981 confers increased susceptibility to lung cancer in Asians.

CASP9 c.‐1339A>G and CASP3 c.‐1191A>G polymorphisms alter susceptibility and clinical aspects of head and neck squamous cell carcinoma

“…In contrast, carriers of CASP9 c.‐1339AA genotype were under increased risk of the lung, bladder, gastric, prostate, and colorectal cancer, and reduced risk of pancreatic and breast cancer. Most of the studies mentioned above were included in a meta‐analysis that showed no association of CASP9 c.‐1339A>G and risk of various types of cancer, giving support to our data.…”

Effects of Caspase 9 Gene Polymorphism in Patients with Prostate Cancer

“…One important property of CASP9 gene polymorphisms is that the incidence can differ substantially among different populations. Their data demonstrated significant differecences in the prevalence of the CASP9 allele between Caucasion and Asians populations (11).…”

Genetic Variation in PDCD6 and Susceptibility to Lung Cancer

“…Current researches show that genetic polymorphisms can explain and contribute to inter-individual differences in oncogenesis and differentiation (Kutikhin 2011;Gu et al, 2012;Nakada et al, 2012;Xu et al, 2012). In 2011, Wei et al (2011).…”