The relationship between central obesity and risk of breast cancer: a dose-response meta-analysis of 7,989,315 women

Abstract

Purpose: Central obesity may contribute to breast cancer (BC); however, there is no dose-response relationship. This meta-analysis examined the effects of central obesity on BC and their potential dose-response relationship.

Methods: In the present study, PubMed, Medline, Embase, and Web of Science were searched on 1 August 2022 for published articles. We included the prospective cohort and case-control studies that reported the relationship between central obesity and BC. Summary effect size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (95% CI) and were evaluated using random-effect models. The inconsistency index (I²) was used to quantify the heterogeneity magnitude derived from the random-effects Mantel-Haenszel model.

Results: This meta-analysis included 57 studies (26 case-control and 31 prospective cohort) as of August 2022. Case-control studies indicated that waist circumference (WC) (adjusted OR = 1.18; 95% CI: 1.00-1.38; P = 0.051) and waist-to-hip ratio (WHR) (adjusted OR = 1.28; 95% CI: 1.07-1.53; P = 0.008) were significantly positively related to BC. Subgroup analysis showed that central obesity measured by WC increased the premenopausal (adjusted OR = 1.15; 95% CI: 0.99-1.34; P = 0.063) and postmenopausal (adjusted OR = 1.18; 95% CI: 1.03-1.36; P = 0.018) BC risk and the same relationship appeared in WHR between premenopausal (adjusted OR = 1.38; 95% CI: 1.19-1.59; P < 0.001) and postmenopausal (adjusted OR = 1.41; 95% CI: 1.22-1.64; P < 0.001). The same relationship was observed in hormone receptor-positive (HR+) (adjusted OR_WC = 1.26; 95% CI: 1.02-1.57; P = 0.035, adjusted OR_WHR = 1.41; 95% CI: 1.00-1.98; P = 0.051) and hormone receptor-negative (HR-) (adjusted OR_WC = 1.44; 95% CI: 1.13-1.83; P = 0.003, adjusted OR_WHR = 1.42; 95% CI: 0.95-2.13; P = 0.087) BCs. Prospective cohort studies indicated that high WC (adjusted RR = 1.12; 95% CI: 1.08-1.16; P < 0.001) and WHR (adjusted RR = 1.05; 95% CI: 1.018-1.09; P = 0.017) may increase BC risk. Subgroup analysis demonstrated a significant correlation during premenopausal (adjusted RR = 1.08; 95% CI: 1.02-1.14; P = 0.007) and postmenopausal (adjusted RR = 1.14; 95% CI: 1.10-1.19; P < 0.001) between BC and central obesity measured by WC, and WHR was significantly positively related to BC both premenopausal (adjusted RR_pre = 1.04; 95% CI: 0.98-1.11; P = 0.169) and postmenopausal (adjusted RR_post = 1.04; 95% CI: 1.02-1.07; P = 0.002). Regarding molecular subtype, central obesity was significantly associated with HR+ (adjusted OR_WC = 1.13; 95% CI: 1.07-1.19; P < 0.001, adjusted OR_WHR = 1.03; 95% CI: 0.98-1.07; P = 0.244) and HR- BCs (adjusted OR_WC =1.11; 95% CI: 0.99-1.24; P = 0.086, adjusted OR_WHR =1.01; 95% CI: 0.91-1.13; P = 0.808). Our dose-response analysis revealed a J-shaped trend in the relationship between central obesity and BC (measured by WC and WHR) in case-control studies and an inverted J-shaped trend between BMI (during premenopausal) and BC in the prospective cohort.

Conclusion: Central obesity is a risk factor for premenopausal and postmenopausal BC, and WC and WHR may predict it. Regarding the BC subtype, central obesity is proven to be a risk of ER+ and ER- BCs. The dose-response analysis revealed that when BMI (during premenopausal) exceeded 23.40 kg/m², the risk of BC began to decrease, and WC higher than 83.80 cm or WHR exceeded 0.78 could efficiently increase the BC risk.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022365788.

Keywords: body mass index; breast cancer; central obesity; hip circumference; meta-analysis; waist circumference; waist-hip-ratio.