title: The TERT variant rs2736100 is associated with colorectal cancer risk.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: B
authors.initials: B
authors.lastname: Kinnersley
authors.forename: G
authors.initials: G
authors.lastname: Migliorini
authors.forename: P
authors.initials: P
authors.lastname: Broderick
authors.forename: N
authors.initials: N
authors.lastname: Whiffin
authors.forename: S E
authors.initials: SE
authors.lastname: Dobbins
authors.forename: G
authors.initials: G
authors.lastname: Casey
authors.forename: J
authors.initials: J
authors.lastname: Hopper
authors.forename: O
authors.initials: O
authors.lastname: Sieber
authors.forename: L
authors.initials: L
authors.lastname: Lipton
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: M G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: I Pm
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000328:Adult; D000368:Aged; D002895:Chromosomes, Human, Pair 5; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*
chemical_list: C116466:CLPTM1 protein, human; D008565:Membrane Proteins; C509186:TERT protein, human; D019098:Telomerase