Circulating adiponectin and breast cancer risk: a systematic review and meta-analysis

Background: We conducted a meta-analysis in order to investigate whether circulating adiponectin, an insulin-sensitizing hormone produced by adipocytes, is associated with breast cancer risk. Methods: A systematic literature search was performed in PubMed, Medline, EMBASE, ISI Web of Knowledge and the Cochrane Library. The summary relative risk (SRR) was calculated by pooling the different study-specific estimates using the random effect models. Meta-regression, subgroup and sensitivity analyses were carried out to investigate between-study heterogeneity and to test publication bias. Results: Data from 15 observational studies, published between 2003 and April 2013 for a total of 4249 breast cancer cases, were analysed. The SRR for the 'highest' vs 'lowest' adiponectin levels indicated a 34% reduction in breast cancer risk [95% confidence interval (CI): 13%-50%]. Between-study heterogeneity was not substantial (I-2 = 53%). Ten studies were included in the dose-response analysis: the SRR for an increase of 3 mu g/ml of adiponectin corresponded to a 5% risk reduction (95% CI: 1%-9%). The comparison between 'highest' and 'lowest' levels of adiponectin showed an inverse association in postmenopausal women (SRR = 0.80; 95% CI: 0.63-1.01) and an indication of an inverse relationship in premenopausal women (SRR = 0.72, 95% CI: 0.30-1.72). No evidence of publication bias was found. Conclusions: Low circulating adiponectin levels are associated with an increased breast cancer risk. However, properly designed studies are needed to confirm the role of adiponectin as breast cancer biomarker, and clinical trials should be performed to identify those interventions that may be effective in modulating adiponectin levels and reducing breast cancer risk.