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The Association Between Smoking, Alcohol and Colon Cancer Survival By KRAS, BRAF, P53 and MSI status: A Molecular Pathology Epidemiology Cohort Study.

Authors

Authors: J Yeo,1 MB Loughrey,2,3 RT Gray,1 S McQuaid,2,4 JA James,2,3,4 M Salto-Tellez,2,3 DB Longley,2 HG Coleman.1,2

Departments / Institutions

1Cancer Epidemiology Research Group, Centre for Public Health, Queen’s University Belfast, 2Centre for Cancer Research and Cell Biology, Queen’s University Belfast 3 Department of Pathology, Belfast Health and Social Care Trust, 4 Northern Ireland Biobank.

Publication Date

Autumn 2018

Introduction

Previous studies have highlighted lifestyle factors in colon cancer survival. Smoking and alcohol may interact with features of tumour biology to influence patient outcomes.

Aims

To investigate the association between smoking status, alcohol intake and colon cancer survival by MSI, P53, KRAS and BRAF status, in a large population-based study.

Methods

Information from 661 patients who underwent surgery for their Stage II or III colon cancer between 2004 and 2008 in Northern Ireland were included. Follow-up and death information was retrieved via linkage to the Northern Ireland Registrar General’s Office up to end 2013. Tissue blocks were retrieved via the Northern Ireland Biobank, and DNA extracted to determine mutations in BRAF, KRAS, P53 and MSI status. The association between lifestyle factors and survival was tested using Cox Proportional Hazard models, adjusting for key confounders.

Results

Smoking was associated with poorer outcomes in colon cancer patients, when investigating both all-cause mortality (HR 1.55, 95% CI 1.17-2.05) and colorectal cancer-specific mortality (HR 1.48, 95%CI 1.05–2.06). Stratified analyses by molecular features found this increased risk of colorectal cancer-specific death to be strongest in patients with MSI-high or P53 mutant tumours (HR 7.21 [95% CI 2.19 – 23.78]) and 1.69 [95% CI 1.10 – 2.56]), respectively. No associations were observed between alcohol intake and survival in colon cancer patients, which did not alter in analyses stratified by molecular subtypes.

Conclusion

Smoking was associated with poorer survival in Stage II and III colon cancer patients, particularly in those with MSI-high or P53 mutant tumours.


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