A pooled analysis of smoking and colorectal cancer: Timing of exposure and interactions with environmental factors

Jian Gong, Carolyn Hutter, John A. Baron, Sonja Berndt, Bette Caan, Peter T. Campbell, Graham Casey, Andrew T. Chan, Michelle Cotterchio, Charles S. Fuchs, Steven Gallinger, Edward Giovannucci, Tabitha Harrison, Richard Hayes, Li Hsu, Shuo Jiao, Yi Lin, Noralane M. Lindor, Polly Newcomb, Bethann PflugeisenAmanda I. Phipps, Thomas Rohan, Robert Schoen, Daniela Seminara, Martha L. Slattery, Deanna Stelling, Fridtjof Thomas, Greg Warnick, Emily White, John Potter, Ulrike Peters

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association. Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors. Results: Current smokers [OR, 1.26; 95% confidence interval (CI), 1.11-1.43] and former smokers (OR, 1.18; 95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04). Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology.

Original languageEnglish
Pages (from-to)1974-1985
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Issue number11
StatePublished - Nov 2012
Externally publishedYes


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