Association between TIM-3 polymorphisms and cancer risk: a meta-analysis

Background: Single nucleotide polymorphisms (SNPs) of T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) were reported to individually associate with cancer risk. To further verify its correlation with human cancers, we evaluated the association of TIM-3 polymorphisms and the risk of cancer. Methods: Data were collected from electronic databases. Two reviewers independently selected studies, extracted data and assessed quality of the studies. Data were meta-analyzed using the STATA 13.0 software. Crude odd ratio (OR) and 95% confidence interval was used to estimate the association between TIM-3 polymorphism and cancer susceptibility. Results: All eligible case-control studies included a total of 4,852 participants (2,229 cases and 2,623 controls). The meta-analysis showed that TIM-3 SNPs (-1516G/T, -574G/T, +4259T/G, and haplotypes) were significantly associated with an increased risk of susceptibility toward all cancers. The subgroup analyses based on cancer types showed that TIM-3 -1516G/T SNP was only associated with an increased risk in developing cancers in the digestive system or in hospital-based populations. Moreover, the TIM-3 -574G/T SNP was associated with an increased cancer risk in the digestive system or other systems, while TIM-3 +4259T/G SNP was only associated with an increased cancer risk in hospital-based populations. Among the four haplotypes observed (GGT, TCT, CGG, and GTT), The GGG haplotype showed an increase in the odds of cancer by 2.614-fold (OR 2.614; 95% CI: 1.756-3.893) compared with the GGT haplotype. Conclusions: TIM-3 SNPs (-1516G/T, -574G/T, +4259T/G and the four haplotypes) were associated with an increased risk of developing human cancers.