DOSE-RESPONSE RELATIONSHIPS BETWEEN CIGARETTE SMOKING AND BREAST CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BackgroundThe possible association between cigarette smoking and breast cancer risk has been quite controversial.MethodsWe 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.ResultsA 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 (i.e., 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 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 and 1.11, 95% CI 1.06-1.16, for 40 years of smoking).ConclusionsThe present large and comprehensive meta-analysis - conducted using an innovative approach for study search - supports the evidence of causal role of tobacco smoking on breast cancer risk.