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Cancer Res. 2018 Aug 15;78(16):4790-4799. doi: 10.1158/0008-5472.CAN-18-0326. Epub 2018 Jun 19.

Influence of Smoking, Body Mass Index, and Other Factors on the Preventive Effect of Nonsteroidal Anti-Inflammatory Drugs on Colorectal Cancer Risk.

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Department of Epidemiology, University of Washington, Seattle, Washington.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Department of Epidemiology, University of Washington, Seattle, Washington.
Centre for Public Health Research, Massey University, Wellington, New Zealand.
Department of Pathology and Laboratory Medicine, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.
Division of General Surgery, Toronto General Hospital, Toronto, Ontario, Canada.
Division of Research, Kaiser Permanente Medical Care Program, Oakland.
Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.


Nonsteroidal anti-inflammatory drugs' (NSAID) use has consistently been associated with lower risk of colorectal cancer; however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on colorectal cancer risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or nonaspirin NSAIDs was significantly associated with a lower risk of colorectal cancer within almost all subgroups. However, smoking status and BMI were found to modify the NSAID-colorectal cancer association. Aspirin use was associated with a 29% lower colorectal cancer risk among never-smokers [odds ratios (OR) = 0.71; 95% confidence intervals (CI): 0.64-0.79], compared with 19% and 17% lower colorectal cancer risk among smokers of pack-years below median (OR, 0.81; 95% CI, 0.71-0.92) and above median (OR, 0.83; 95% CI, 0.74-0.94), respectively (P interaction = 0.048). The association between any NSAID use and colorectal cancer risk was also attenuated with increasing BMI (P interaction = 0.075). Collectively, these results suggest that obese individuals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against colorectal cancer.Significance: Obesity and heavy smoking attenuate the benefit of aspirin use for colorectal cancer prevention. Cancer Res; 78(16); 4790-9. ©2018 AACR.

[Available on 2019-08-15]

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