Central obesity and risks of pre- and postmenopausal breast cancer: a dose-response meta-analysis of prospective studies.

Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist-to-hip ratio (WHR), and risks of pre- and postmenopausal breast cancer (BC). A dose-response meta-analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10-cm increase = 1.06, 95% CI: 1.04-1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1-unit increase = 1.07, 95% CI: 1.01-1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10-cm increase = 1.05, 95% CI: 0.99-1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1-unit increase = 1.07, 95% CI: 0.95-1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR-postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1-unit increase = 1.06, 95% CI: 0.99-1.13). When considering BMI-adjusted RRs, WC was associated with both pre- (five studies, RR per 10-cm increase = 1.09, 95% CI: 1.02-1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10-cm increase = 1.05, 95% CI: 1.02-1.08, I2 = 6.3%), whereas WHR was not associated with either pre- (seven studies, RR per 0.1-unit increase = 1.12, 95% CI: 0.94-1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1-unit increase = 1.05, 95% CI: 0.98-1.13, I2 = 57.3%). Among non-current (former or never) users of hormone replacement therapy, the summary RR per 10-cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03-1.05, I2 = 69.2%, seven studies; BMI-adjusted RR = 1.05, 95% CI: 1.02-1.09, I2 = 22.8%, four studies). This meta-analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre- and postmenopausal BC independent of general obesity.