Association between the TERT Genetic Polymorphism rs2853676 and Cancer Risk: Meta-Analysis of 76,108 Cases and 134,215 Controls

PLoS One. 2015 Jun 4;10(6):e0128829. doi: 10.1371/journal.pone.0128829. eCollection 2015.

Abstract

Background: Several recent studies have identified that the TERT genetic polymorphism rs2853676 is associated with cancer risk, but presented inconsistent results. We investigated these inconclusive results by performing a meta-analysis to systematically evaluate the association.

Methods: We conducted a search in PubMed, Google Scholar and ISI Web of Science to select studies on the association between TERT rs2853676 and cancer risk. We conducted a stratified analysis using cancer type, ethnicity and source of controls. We calculated the odds ratios (OR) and 95% confidence intervals (CI). Article quality, heterogeneity, sensitivity, publication bias and statistical power were also assessed.

Results: 26 articles covering 76,108 cases and 134,215 controls met our inclusion criteria. A significant association between TERT rs2853676 allele A and cancer susceptibility was demonstrated under a per-allele risk analysis (OR = 1.08, 95% CI = 1.04-1.13). Stratification analysis revealed an increased cancer risk in subgroups of glioma, lung cancer and ovarian cancer. No significant increase was found in melanoma, breast cancer, pancreatic cancer and colorectal cancer. In a subgroup analysis of lung cancer, a statistically significant increase was only observed in adenocarcinoma. Moreover, a stratified analysis performed for ethnic groups revealed that the significant increase was only observed in Caucasians, whereas a non-significant increase was found in Asians.

Conclusions: This meta-analysis suggests that the TERT genetic polymorphism rs2853676 is associated with increased risk of glioma, lung adenocarcinoma and ovarian cancer among Caucasians. Further functional studies are warranted to validate this association and investigate further.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma of Lung
  • Case-Control Studies
  • Databases, Genetic
  • Genetic Association Studies*
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Humans
  • Lung Neoplasms / genetics
  • Odds Ratio
  • Oxidoreductases Acting on CH-CH Group Donors / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Publication Bias
  • Risk Factors

Substances

  • Oxidoreductases Acting on CH-CH Group Donors
  • trans-2-enoyl-CoA reductase (NADPH)

Grants and funding

This work was supported by the National Natural Science Foundation of China (NSFC 31170720). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.