The TERT variant rs2736100 is associated with colorectal cancer risk

Colon Canc Family Registry, CORGI Consortium, B. Kinnersley, G. Migliorini, P. Broderick, N. Whiffin, S. E. Dobbins, G. Casey, J. Hopper, O. Sieber, L. Lipton, D. J. Kerr, M. G. Dunlop, I. P. M. Tomlinson, R. S. Houlston*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 x 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 x 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.

Original languageEnglish
Pages (from-to)1001-1008
Number of pages8
JournalBritish Journal of Cancer
Volume107
Issue number6
DOIs
Publication statusPublished - 4 Sep 2012

Keywords

  • GENOME-WIDE ASSOCIATION
  • TERT-CLPTM1L LOCUS
  • SUSCEPTIBILITY LOCI
  • rs2736100
  • DMRT1
  • 5P15.33
  • colorectal cancer
  • PREDISPOSE
  • SCAN
  • METAANALYSIS
  • TERT-CLPTM1L
  • BREAST-CANCER
  • POLYMORPHISMS

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