Lifestyle factors, medications and colon cancer survival stratified by biomarkers

: A molecular cancer epidemiology approach

Abstract

Colorectal cancer (CRC) has a complex multi-mechanistic and multi-factorial aetiology, with different tumours having distinct genomic and epigenomic alterations. Tumours with similar characteristics, on the other hand, can be classified together due to their presumed common development mechanism. Traditionally this classification has been solely on the basis of tumour morphology. Molecular understanding of CRC has improved significantly in recent years, culminating in a proposed consensus molecular classification of CRC, but we still do not fully comprehend the interactions between molecular biomarkers, commonly used medications, and lifestyle factors on survival outcomes.

For these reasons, the overall aim of this thesis was to examine how specific molecular and immune biomarkers, and exposures (including commonly used medications, lifestyle factors) interact to influence survival of colon cancer patients within a large population-based cohort.In summary, subgroups of patients who are tobacco smokers appear to have poorer prognosis according to their molecular characteristics; the evidence is less consistent for alcohol use. Preliminary evidence for deleterious association between ARB use and patients with MSS status tumours requires further investigate to optimise patient safety and outcomes. A large resource has been created to enable future transcriptional biomarker studies that would also address a major gap in molecular pathology epidemiology (MPE) cancer studies. Such clarification of molecular and immune specific associations between lifestyle factors, medications and CRC survival would help to inform analysis strategies for ongoing trials in this subject and would also guide the design of targeted stratified trials in the future.

Thesis embargoed until 31 December 2023

Date of Award	Dec 2022
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Directorate General of Higher Foreign Education, the Ministry of National Education in Turkey
Supervisor	Philip Dunne (Supervisor) & Helen Coleman (Supervisor)