Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer

Jayasekara, Harindra, MacInnis, Robert J., Williamson, Elizabeth J., Hodge, Allison M., Clendenning, Mark, Rosty, Christophe, Walters, Rhiannon, Room, Robin, Southey, Melissa C., Jenkins, Mark A., Milne, Roger L., Hopper, John L., Giles, Graham G., Buchanan, Daniel D. and English, Dallas R. (2017) Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer. International Journal of Cancer, 140 7: 1485-1493. doi:10.1002/ijc.30568

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Author Jayasekara, Harindra
MacInnis, Robert J.
Williamson, Elizabeth J.
Hodge, Allison M.
Clendenning, Mark
Rosty, Christophe
Walters, Rhiannon
Room, Robin
Southey, Melissa C.
Jenkins, Mark A.
Milne, Roger L.
Hopper, John L.
Giles, Graham G.
Buchanan, Daniel D.
English, Dallas R.
Title Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer
Formatted title
Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 1097-0215
0020-7136
Publication date 2017-04-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/ijc.30568
Open Access Status File (Author Post-print)
Volume 140
Issue 7
Start page 1485
End page 1493
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40–69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04–1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00–1.15) and BRAF−/KRAS− (HR = 1.05, 95% CI: 1.00–1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78–1.01; phomogeneity = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF−/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway.
Keyword Alcohol intake
BRAF
Colorectal cancer
KRAS
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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