Lack of association between cytotoxic T-lymphocyte antigen-4 -318C/T polymorphism and cancer risk: a meta-analysis of case-control studies.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is important for the down regulation of T-cell activation. Number of studies assessed the association between CTLA-4 -318C/T polymorphisms and cancer in different populations. However, the studies have provided conflicting results. We performed a meta-analysis to examine the association between CTLA-4 -318C/T polymorphisms and cancer susceptibility. Eligible studies were identified by searching several databases for relevant reports published up to September 30, 2012. Sixteen eligible studies with a total of 6190 patients and 6560 controls were included to summarize the association between CTLA-4 -318C/T polymorphisms and the risk of cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Overall, no significant associations were found in all genetic models when all studies were pooled into the meta-analysis (for -318C/T polymorphisms as estimated using a fixed effect model: TT vs. (CC + CT), OR = 1.02, 95% CI = 0.83-1.24; (TT + CT) vs. CC, OR = 1.20, 95% CI = 1.00-1.44; TT vs. CC, OR = 1.09, 95% CI = 0.74-1.59; CT vs. CC, OR = 1.21, 95% CI = 1.00-1.46). In further subgroup analyses for the -318C/T polymorphisms, stratified by design of ethnicity, cancer types, solid tumors to non-solid tumors, epithelial tumors to non-epithelial tumors, no significant associations were found in any subgroup of the population. This meta-analysis strongly suggests that -318C/T polymorphisms in CTLA-4 are not associated with an increased risk of cancer.