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Br J Cancer. 2018 Mar 6;118(5):727-732. doi: 10.1038/bjc.2017.486. Epub 2018 Feb 13.

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

Author information

1
Molecular and Population Genetics Laboratory University of Oxford, Oxford OX3 7BN, UK.
2
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Old Road Campus, Oxford OX3 7DQ, UK.
3
Ludwig Institute for Cancer Research, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
4
Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
5
Gastrointestinal Stem Cell Biology Laboratory, Oxford Centre for Cancer Gene Research and.
6
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.

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.

PMID:
29438375
PMCID:
PMC5846076
DOI:
10.1038/bjc.2017.486
[Indexed for MEDLINE]
Free PMC Article

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