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/m 2 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/m 2 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.