TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12-1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15-1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16-1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05-1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04-1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10-1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.