Meta-analysis of smoking and breast cancer risk: by age of smoking initiation

Background: Mounting evidence suggests that smoking increases breast cancer risk. Despite a worldwide increase in adolescent smoking, potential heterogeneity in the relationship by timing of smoking initiation has not been systematically evaluated. Methods: PubMed and Embase were searched through January 2024 for relevant epidemiologic studies. The summary relative risk (SRR) and 95% confidence interval (CI) were estimated by smoking initiation age (≤ 15 years, 15–20 years, ≥ 20 years) using the DerSimonian-Laird random-effects model. Results: A total of 30 case–control studies and 20 cohort studies were included. The SRR was 1.08 (95% CI = 1.02–1.14, p < 0.05, I² = 54%) for smoking initiated at age ≤ 15 years, 1.10 (95% CI = 1.07–1.14, p < 0.001, I² = 32%) for smoking initiated at age 15–20 years, and 1.08 (95% CI = 1.04–1.12, p < 0.001, I² = 42%) for smoking initiated at age ≥ 20 years. When timing of smoking initiation was defined relative to first childbirth, SRR was 1.10 (95% CI = 1.05–1.15, p < 0.001, I² = 34%) for smoking initiated before first childbirth, and 1.05 (95% CI = 0.99–1.11, p = 0.13, I² = 39%) for smoking initiated after first childbirth. Conclusions: Smoking, regardless of age of initiation, may increase breast cancer risk. More studies are warranted to clarify how the timing of smoking initiation relative to first childbirth modifies the relationship between smoking and breast cancer risk.