Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel

Ceres Fernandez-Rozadilla, Christiana Kartsonaki, Connor Woolley, Michael McClellan, Deb Whittington, Gareth Horgan, Simon Leedham, Skirmantas Kriaucionis, James East, Ian Tomlinson

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors.

METHODS: We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms.

RESULTS: Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations.

CONCLUSIONS: PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

Original languageEnglish
Pages (from-to)727-732
Number of pages6
JournalBritish Journal of Cancer
Volume118
Issue number5
DOIs
Publication statusPublished - 13 Feb 2018

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/genetics
  • Case-Control Studies
  • Colon/chemistry
  • Colonoscopy
  • Colorectal Neoplasms/diagnosis
  • DNA Methylation
  • Early Detection of Cancer
  • Female
  • Gene Regulatory Networks
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Rectum/chemistry
  • Risk Factors
  • Telomere Homeostasis
  • Young Adult

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