Early-life body mass index and risks of breast, endometrial, and ovarian cancers: a dose–response meta-analysis of prospective studies

Background: The evidence for the associations between early-life adiposity and female cancer risks is mixed. Little is known about the exact shape of the relationships and whether the associations are independent of adult adiposity. Methods: We conducted dose–response meta-analyses of prospective studies to summarise the relationships of early-life body mass index (BMI) with breast, endometrial, and ovarian cancer risks. Pubmed and Embase were searched through June 2020 to identify relevant studies. Using random-effects models, the summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated per 5-kg/m² increase in BMI at ages ≤ 25 years. A nonlinear dose–response meta-analysis was conducted using restricted cubic spline analysis. Results: After screening 33,948 publications, 37 prospective studies were included in this analysis. The summary RRs associated with every 5-kg/m² increase in early-life BMI were 0.84 (95% CI = 0.81–0.87) for breast, 1.40 (95% CI = 1.25–1.57) for endometrial, and 1.15 (95% CI = 1.07–1.23) for ovarian cancers. For breast cancer, the association remained statistically significant after adjustment for adult BMI (RR = 0.80, 95% CI = 0.73–0.87). For premenopausal breast, endometrial, and ovarian cancers, the dose–response curves suggested evidence of nonlinearity. Conclusions: With early-life adiposity, our data support an inverse association with breast cancer and positive associations with ovarian and endometrial cancer risks.