Associations of adipokines & insulin resistance with sex steroids in patients with breast cancer
ABSTRACT Several studies have suggested an important, but conflicting and controversial role for adipose tissue mass in breast cancer risk. Factors such as insulin-like growth factors, sex steroids, adipokines and obesity-related inflammatory markers have been postulated as potential effectors of the mechanisms by which obesity and associated metabolic disorders influence breast cancer risk. In this study we evaluated the associations between obesity indices, insulin resistance, circulating adipokines, sex steroids and breast cancer.
Fasting adiponectin, leptin, insulin resistance (homeostasis model assessment, HOMA-IR), testosterone, estradiol, sex hormone binding globulin (SHBG), LH and FSH were determined in 144 newly-diagnosed histologically confirmed breast cancer patients and 77 controls. Univariate and multivariate regression analyses were used to find the associations of these variables with each other, indices of obesity and with breast cancer.
BMI, waist circumference, HOMA-IR and leptin were significantly (P<0.001) higher in patients than in controls. Adiponectin level was also significantly (P<0.05) higher in patients compared to controls. Adiponectin and leptin showed significant correlations with insulin and HOMA-IR but only adiponectin was significantly correlated with estradiol and SHBG. Logistic regression analyses showed that factors associated with breast cancer were BMI [OR (95% CI) =2.8 (1.4-5.5), P=0.004]; high levels of adiponectin [5.1 (2.2-11.5), P<0.001); hyperinsulinaemia [1.1 (1.0-1.1), P=0.01], leptin [3.1 (1.7-5.7), P<0.0001], estradiol [2.5 (1.3-4.7), P=0.005] and testosterone [1.3 (1.03-1.7), P=0.03].
Our findings confirm that adipokines, insulin resistance and sex steroids are associated with breast cancer. The paradoxical association of increased adiponectin with breast cancer is a novel finding that deserves further investigation.
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ABSTRACT: Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling.Clinics in liver disease 02/2014; 18(1):41-58. DOI:10.1016/j.cld.2013.09.012
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ABSTRACT: Abstract Background: Conclusive evidence has yet to emerge regarding the association between markers of hyperinsulinemia and breast cancer. We determined the effect of insulin resistance (IR) on breast cancer risk in Latinas of Mexican origin who did not have a direct family history of breast cancer and had not been previously diagnosed with prediabetes or diabetes. Methods: This was a case-control study in which a case (n=124) was defined as a patient with a recent histopathologic diagnosis of breast cancer and a control (n=197) was defined as a participant who had recently undergone a mammography and had either a Breast Imaging, Reporting & Data System (BI-RADS)-1 or a BI-RADS-2 score. Plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured. IR was determined by using the homeostasis model assessment (HOMA-IR) criterion. Odds ratios (OR) and 95% confidence intervals (CI) were determined using unconditional binary logistic regression analysis. Results: IR was detected in 33.9% of cases and 41.6% of controls, based on a HOMA-IR ≥3.5. Although multivariate analysis did not show any association between IR and breast cancer risk (OR 0.56, 95% CI 0.31-1.01), it showed that an HbA1c ≥5.7% increased the risk of breast cancer (OR 3.41, 95% CI 1.93-6.01), regardless of menopausal status. Conclusions: The findings suggest that IR had no effect on breast cancer risk; however HbA1c increased the risk in Latinas of Mexican origin who had not been diagnosed previously with prediabetes or diabetes and had no direct family history of breast cancer. Prospective studies are required to establish the impact of IR over time.Metabolic Syndrome and Related Disorders 08/2014; DOI:10.1089/met.2014.0071 · 1.92 Impact Factor
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ABSTRACT: 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. 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. 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 µg/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 = 0.70; 95% CI: 0.28-1.76). No evidence of publication bias was found. 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.International Journal of Epidemiology 04/2014; 43(4). DOI:10.1093/ije/dyu088 · 9.20 Impact Factor