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BackgroundPolymorphic 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.MethodsWe 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.Resultsrs2736100, 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.ConclusionThe 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 publication

DOI

10.1038/bjc.2012.329

Type

Journal article

Journal

British journal of cancer

Publication Date

09/2012

Volume

107

Pages

1001 - 1008

Addresses

Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.

Keywords

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