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

Abstract

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.

Fig. 1. Linear and nonlinear dose–response relationships for early-life BMI and breast cancer risk.

This figure shows the results from a linear dose–response relationship with total breast cancer; b nonlinear dose–response relationship with total breast cancer (p-nonlinearity = 0.19); c subgroup analysis by menopausal status (p-heterogeneity = 0.78); d nonlinear dose–response relationship with premenopausal breast cancer (p-nonlinearity = 0.004); e nonlinear dose–response relationship with postmenopausal breast cancer (p-nonlinearity = 0.16); f subgroup analysis by adjustment for adult BMI (p-heterogeneity = 0.36). The black squares and horizontal lines represent study-specific relative risks and their 95% confidence intervals. The area of each black square reflects the weight each study contributes to the meta-analysis. The middle and horizontal tips of diamonds represent summary RRs and their 95% confidence intervals, respectively. The P values were calculated from Cochran’s Q test; all statistical tests were two-sided.

Fig. 2. Linear and nonlinear dose–response relationships for early-life BMI and endometrial cancer risk.

This figure shows the results from a linear dose–response relationship with endometrial cancer; b nonlinear dose–response relationship with endometrial cancer (p-nonlinearity = 0.004); c subgroup analysis by adjustment for adult BMI (p-heterogeneity = 0.19). The black squares and horizontal lines represent study-specific relative risks and their 95% confidence intervals. The area of each black square reflects the weight each study contributes to the meta-analysis. The middle and horizontal tips of diamonds represent summary RRs and their 95% confidence intervals, respectively. The P values were calculated from Cochran’s Q test; all statistical tests were two-sided.

Fig. 3. Linear and nonlinear dose–response relationships for early-life BMI and ovarian cancer risk.

This figure shows the results from a linear dose–response relationship with ovarian cancer; b nonlinear dose–response relationship with ovarian cancer (p-nonlinearity = 0.05). The black squares and horizontal lines represent study-specific relative risks and their 95% confidence intervals. The area of each black square reflects the weight each study contributes to the meta-analysis. The middle and horizontal tips of diamonds represent summary RRs and their 95% confidence intervals, respectively. The P values were calculated from Cochran’s Q test; all statistical tests were two-sided.