Associations between Smoking, Alcohol Consumption, and Colorectal Cancer, Overall and by Tumor Microsatellite Instability Status

Introduction: Both smoking and alcohol consumption have been associated with modestly increased risks of colorectal cancer (CRC). Reports have suggested that these associations may differ by tumor molecular subtype, with stronger associations for microsatellite unstable (MSI-H) tumors. Methods: We u...

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Published in:	Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2009-10, Vol.18 (10), p.2745-2750
Main Authors:	POYNTER, Jenny N, HAILE, Robert W, CASEY, Graham, HOPPER, John L, JENKINS, Mark A, THIBODEAU, Stephen N, NEWCOMB, Polly A, BARON, John A, SIEGMUND, Kimberly D, CAMPBELL, Peter T, FIGUEIREDO, Jane C, LIMBURG, Paul, YOUNG, Joanne, LE MARCHAND, Loic, POTTER, John D, COTTERCHIO, Michelle
Format:	Article
Language:	eng
Subjects:	Adult alcohol consumption Alcohol Drinking - adverse effects Alcohol Drinking - epidemiology Alcohol Drinking - genetics Biological and medical sciences cigarette smoking colorectal cancer Colorectal Neoplasms - epidemiology Colorectal Neoplasms - genetics DNA Mismatch Repair Female Humans Male Medical sciences Microsatellite Instability Middle Aged Registries Risk Factors Smoking - adverse effects Smoking - epidemiology Smoking - genetics Tobacco, tobacco smoking Toxicology Tumors Young Adult
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Summary:	Introduction: Both smoking and alcohol consumption have been associated with modestly increased risks of colorectal cancer (CRC). Reports have suggested that these associations may differ by tumor molecular subtype, with stronger associations for microsatellite unstable (MSI-H) tumors. Methods: We used a population-based case-unaffected sibling design including 2,248 sibships (2,253 cases; 4,486 siblings) recruited to the Colon Cancer Family Registry to evaluate the association between smoking, alcohol consumption, and CRC. Associations were assessed using conditional logistic regression, treating sibship as the matching factor. Results: Although there were no statistically significant associations between any smoking variable and CRC overall, smoking did confer an increased risk of certain types of CRC. We observed an association between pack-years of smoking and rectal cancer [odds ratio (OR), 1.85; 95% confidence interval (CI), 1.23-2.79 for >40 pack-years versus nonsmokers; P trend = 0.03], and there was an increased risk of MSI-H CRC with increasing duration of smoking (OR, 1.94; 95% CI, 1.09-3.46 for >30 years of smoking versus nonsmokers). Alcohol intake was associated with a modest increase in risk for CRC overall (OR, 1.21; 95% CI, 1.03-1.44 for 12+ drinks per week versus nondrinkers), with more marked increases in risk for MSI-L CRC (OR, 1.85; 95% CI, 1.06-3.24) and rectal cancer (OR, 1.48; 95% CI, 1.08-2.02). Conclusions: We found associations between cigarette smoking and increased risks of rectal cancer and MSI-H CRC. Alcohol intake was associated with increased risks of rectal cancer and MSI-L CRC. These results highlight the importance of considering tumor phenotype in studies of risk factors for CRC. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2745–50)
ISSN:	1055-9965 1538-7755