TERT-CLPTM1L polymorphism rs401681 contributes to cancers risk: evidence from a meta-analysis based on 29 publications

PLoS One. 2012;7(11):e50650. doi: 10.1371/journal.pone.0050650. Epub 2012 Nov 30.

Abstract

Background: Some common genetic variants of TERT-CLPTM1L gene, which encode key protein subunits of telomerase, have been suggested to play a crucial role in tumorigenesis. The TERT-CLPTM1L polymorphism rs401681 was of special interest for cancers risk but with inconclusive results.

Methodology/principal findings: We performed a comprehensive meta-analysis of 29 publications with a total of 91263 cases and 735952 controls. We assessed the strength of the association between rs401681 and overall cancers risk and performed subgroup analyses by cancer type, ethnicity, source of control, sample size and expected power. Rs401681 C allele was found to be associated with marginally increased cancers risk, with per allele OR of 1.04 (95%CI = 1.00-1.08, P(heterogeneity)<0.001) and an expected power of 1.000. Following further stratified analyses, the increased cancers risk were discovered in subgroups of lung, bladder, prostate, basal cell carcinomas and Asians, while a declined risk of pancreatic cancer and melanoma were detected.

Conclusions/significance: These findings suggested that rs401681 C allele was a low-penetrance risk allele for the development of cancers of lung, bladder, prostate and basal cell carcinoma, but a potential protective allele for melanoma and pancreatic cancer.

Publication types

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

MeSH terms

  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Neoplasms / enzymology*
  • Neoplasms / genetics*
  • Polymorphism, Genetic*
  • Telomerase / genetics*

Substances

  • CLPTM1L protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Telomerase

Grants and funding

This work was supported by the National Natural Science Foundation of China (NSFC 30972534, NSFC 81172752, and NSFC 81172754) and Natural Science Foundation of Hubei Province (2011CDB203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.