The TERT variant rs2736100 is associated with colorectal cancer risk

Br J Cancer. 2012 Sep 4;107(6):1001-8. doi: 10.1038/bjc.2012.329. Epub 2012 Aug 9.

Abstract

Background: Polymorphic variation at the 5p15.33 (TERT-CLPTM1L) locus is associated with the risk of many cancers but a relationship with colorectal cancer (CRC) risk has yet to be defined.

Methods: We used data from six genome-wide association studies (GWAS) of CRC, linkage disequilibrium mapping and imputation, to examine the relationship between 73 single-nucleotide polymorphisms at 5p15.33 and CRC risk in detail.

Results: rs2736100, which localises to intron 2 of TERT, provided the strongest evidence of an association with CRC (P=2.28 × 10⁻⁴). The association was also shown in an independent series of 10 047 CRC cases and 6918 controls (P=0.02). A meta-analysis of all seven studies (totalling 16 039 cases, 16 430 controls) provided increased evidence of association (P=2.49 × 10⁻⁵; per allele odds ratio=1.07). The association of rs2736100 on CRC risk was shown to be independent of 15 low-penetrance variants previously identified.

Conclusion: The rs2736100 association demonstrates an influence of variation at 5p15.33 on CRC risk and further evidence that the 5p15.33 (TERT-CLPTM1L) locus has pleiotropic effects (reflecting generic or lineage-specific effects) on cancer risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human, Pair 5*
  • Colorectal Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Telomerase / genetics*

Substances

  • CLPTM1 protein, human
  • Membrane Proteins
  • TERT protein, human
  • Telomerase