A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility

Caspases 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.

We 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).

Our 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.