Dose-response Relationships Between Cigarette Smoking and Breast Cancer Risk: A Systematic Review and Meta-analysis

Background: The possible association between cigarette smoking and breast cancer risk has been quite controversial. Methods: We conducted a systematic review and meta-analysis of all available observational studies published on the issue up to January 2020. Random-effects models were used to compute pooled relative risks (RRs) for cigarette smoking status and dose-risk relationships were evaluated using one-stage random-effects dose-response models. Results: A total of 169 studies were selected, providing a pooled RR for breast cancer of 1.07 (95% confidence interval [CI], 1.05–1.10) for current, 1.08 (95% CI, 1.06–1.10) for former, and 1.09 (95% CI, 1.07–1.11) for ever smokers, compared to never smokers. Results were consistent in case-control and cohort studies. No meaningful differences were observed across strata of most covariates considered, nor according to relevant genetic mutations and polymorphisms (ie, BRCA mutation, N-acetyltransferase and glutathione S-transferase genotypes, and P53). Breast cancer risk increased linearly with intensity of smoking (RR 1.12; 95% CI, 1.08–1.16 for 20 cigarettes/day and 1.26; 95% CI, 1.17–1.36 for 40 cigarettes/day), and with increasing duration of smoking (RR 1.05; 95% CI, 1.03–1.08 for 20 years of smoking and 1.11; 95% CI, 1.06–1.16 for 40 years of smoking). Conclusion: The present large and comprehensive meta-analysis—conducted using an innovative approach for study search— supports the evidence of a causal role of tobacco smoking on breast cancer risk.