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

Abstract

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.

Figure 1

Forest plot for smoking status (ever vs. never) and risk of (a) colorectal cancer, (b) colon cancer, and (c) rectum cancer ; adjusted for age, sex, BMI (<25, 25–<30), ≥30 kg/m2), education (high school graduate or less, some college or technical school, and college graduate or higher), alcohol intake (0–1 g/day, 1<−28 g/day, >28 g/day, when available), and study site (if applicable); RE model: random effect model.

Figure 2

Nonparametric regression curve for the association between time since quit smoking and risk of (a) colorectal cancer, (b) proximal colon cancer, (c) distal colon cancer, and (d) rectal cancer; never smokers were excluded; current smoker was assigned to 0 and used as reference group; stratified by study and additionally adjusted for age, sex, BMI (<25, 25–<30), ≥30 kg/m2), education (high school graduate or less, some college or technical school, and college graduate or higher), and pack-years (≤20, 21–40, 41–60, >60 pack-years); solid line is regression curve and dotted line is 95% confidence interval).