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

Fernandez-Rozadilla C., Kartsonaki C., Woolley C., McClellan M., Whittington D., Horgan G., Leedham S., Kriaucionis S., East J., Tomlinson I.

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.

DOI

10.1038/bjc.2017.486

Type

Journal article

Journal

British Journal of Cancer

Publisher

Springer Science and Business Media LLC

Publication Date

06/03/2018

Volume

118

Pages

727 - 732

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