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

J Epidemiol. 2023 Dec 5;33(12):640-648. doi: 10.2188/jea.JE20220206. Epub 2023 Oct 31.


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.

Keywords: breast cancer; meta-analysis; risk; systematic review; tobacco smoking.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / etiology
  • Cigarette Smoking*
  • Cohort Studies
  • Female
  • Humans
  • Japan
  • Risk Factors