Caspase-8 Polymorphism and Colorectal Cancer Risk: A Meta-Analysis of 35,854 Subjects

Abstract

Objective Caspase-8 (CASP8) is essential for apoptotic clearance of transformed cells and is encoded by the CASP8 gene. The CASP8 -652 6N del polymorphism (rs3834129) has been studied in relation to colorectal cancer (CRC) risk with conflicting outcomes. This meta-analysis aims to provide a consolidated assessment of the association between rs3834129 and susceptibility to CRC. Methods Eligible case-control studies published up to January 2025 were systematically retrieved from PubMed, Web of Science, and China National Knowledge Infrastructure. For each study, the association of the CASP8 -652 6N del polymorphism with CRC risk was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 22 studies derived from 12 eligible articles involving 15,327 patients with CRC and 20,527 control subjects were enrolled in this meta-analysis. Collectively, the CASP8 -652 6N del variant correlated with reduced CRC risk under the heterozygote genetic model (OR=0.94, 95% CI: 0.89-0.99). When stratifying analyses according to ethnic background, comparable protective associations were detected within Asian populations. By contrast, no statistically meaningful link was identified between this polymorphism and CRC susceptibility among Caucasian individuals. Further stratification based on tumor site revealed no significant correlations for either colon cancer or rectal cancer subgroups. Conclusions This meta-analysis provides evidence that the CASP8 -652 6N del polymorphism may be linked to a moderately decreased risk of CRC in Asian subjects.