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

Research output: Contribution to journalArticle

Authors

  • Ceres Fernandez-rozadilla
  • Christiana Kartsonaki
  • Connor Woolley
  • Michael Mcclellan
  • Deb Whittington
  • And 5 others
  • Gareth Horgan
  • Simon Leedham
  • Skirmantas Kriaucionis
  • James East
  • Ian Tomlinson

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)727-732
JournalBritish Journal of Cancer
Volume118
Issue number5
Early online date13 Feb 2018
Publication statusPublished - 6 Mar 2018