Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta‐analysis of epidemiologic studies

Abstract

We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin-leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case-control and eight case-control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34-0.65; I 2 5 63.7%; n 5 13), 2.19 (95% CI: 1.44-3.31; I 2 5 64.2%; n 5 7),and 0.45 (95% CI: 0.24-0.86; I 2 5 90.1%; n 5 5), respectively. Notably, there was an 18% reduction in risk for per each 5 lg/mL increment in circulating adiponectin concentrations (SOR 5 0.82; 95% CI: 0.74-0.90; I 2 5 49%; n 5 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this metaanalysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.Endometrial cancer is the second most common gynecologic malignancy worldwide, with approximately 0.3 million new cases in 2012. 1 There is no doubt that obesity is a wellrecognized risk factor for this disease. Recently, the biological mechanisms linking obesity and endometrial cancer have largely centered on the aromatization of androgens in adipose tissue, leading to increased circulating estradiol levels 2 which have been the primary stimulants of endometrial proliferation. 3 However, this mechanism cannot fully explain the incidence of endometrial cancer in obese women. Experimental studies have provided evidence that adipokines, which are associated with hyperinsulinemia and degree of insulin resistance independent of adiposity, are also involved in the development of endometrial cancer.Adipose tissue was previously considered to be an energystorage site. During recent decades, this tissue has been found to be an endocrine organ producing and secreting several bioactive peptides, including adipokines such as adiponectin and leptin. 4 Biological studies have shown that adiponectin, the most abundant adipokine, is not only inversely associated with obesity as well as hyperinsulinemia 5,6 but appears to have anti-inflammatory, antiangiogenic and antidiabetic properties 7,8 ; In contrast,...

Association between Leptin, Adiponectin, and Leptin/Adiponectin Ratio with Clustered Metabolic Risk Factors in Portuguese Adolescents: The LabMed Physical Activity Study

“…Some comparative studies were carried out to investigate the strength of adiponectin, leptin, and the L/A ratio in predicting outcomes such as metabolic syndrome [10,11], insulin resistance [39], and cancer [40]. We have demonstrated that the L/A ratio shows higher association values with MRF than leptin or adiponectin, similar to previous studies with adults.…”

“…We have demonstrated that the L/A ratio shows higher association values with MRF than leptin or adiponectin, similar to previous studies with adults. It has also been shown that increased circulating adiponectin and A/L ratio (the inverse ratio used in the present study) or decreased leptin levels were associated with a reduced risk of endometrial cancer [40]. …”

Evolving role of adiponectin in cancer-controversies and update

“…A significant inverse relationship has been found between APN levels and EC risk [93][94][95][96][97] , as well as between the LAR ratio and EC risk 97 . In particular, one recent meta-analysis showed that higher APN levels were associated with a 53% reduction in EC risk 93 .…”

Identifying High-Risk Women for Endometrial Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk Prediction Model

“…It is also able to increase apoptosis by inducing expression of p53 and Bax, thereby acting as a negative regulator of tumor formation (23). Higher serum levels of adiponectin are associated with a reduction in endometrial cancer risk (summary: OR, 0.47; 95% CI, 0.34-0.65) with evidence of a dose-response relationship (24). For each 5 mg/mL increase in adiponectin levels, the risk of endometrial cancer has been found to decrease by 18%, an effect consistent across analyses adjusted for confounding factors, such as menopausal status, BMI, and hormone replacement therapy (HRT) use.…”