The individual and combined effects of alcohol consumption and cigarette smoking on site-specific cancer risk in a prospective cohort of 26,607 adults: results from Alberta's Tomorrow Project.

Purpose: Alcohol consumption and cigarette smoking increase the risk of developing several cancers. We examined the individual and synergistic effects of these modifiable lifestyle factors on overall and site-specific cancer risk.

Methods: Baseline participant data were acquired from Alberta's Tomorrow Project (ATP). Adults 35-69 years old who consented to data linkage and completed relevant questionnaires were included (n = 26,607). Incident cases of cancer up to December 2017 were identified via linkage to the Alberta Cancer Registry. Associations between alcohol consumption, cigarette smoking, and cancer risk were examined using adjusted Cox proportional hazard models. Non-linear effects were estimated using restricted cubic splines. Interactions between alcohol and tobacco were examined through stratified analyses and inclusion of interaction terms in relevant models.

Results: A total of 2,370 participants developed cancer during the study follow-up period. Cox proportional hazard models found no statistically significant associations between alcohol consumption and incidence of all cancers among males (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.93-1.40) and females ([HR] 0.89, 95% confidence interval [CI] 0.73-1.10), though a modest and positive association was observed in both males and the entire cohort using cubic splines. Smokers were at an increased risk of developing all cancers (female current smokers: [HR] 1.72, 95% [CI] 1.49-1.99, male current smokers: [HR] 1.24, 95% [CI] 1.03-1.49) with the strongest association observed between current smokers and lung cancer (males: [HR] 11.33, 95% [CI] 4.70-27.30, females: [HR] 23.51, 95% [CI] 12.70-43.60). A 3-way interaction model showed an additive effect between alcohol as a continuous variable (g/day) and pack-years (PYs) consumed for all, colon, and prostate cancers. A "U-shaped" multiplicative interaction was observed for breast cancer (p = 0.05).

Conclusions: Alcohol consumption was minimally associated with all-cancer risk. Cigarette smoking clearly increased all-cancer risk, with females being more affected than males. Combined use of alcohol and tobacco increased the risk of developing all, colon, and prostate cancers. A "U-shaped" multiplicative interaction was observed for breast cancer when alcohol and tobacco were used in combination.