Associations of adipokines & insulin resistance with sex steroids in patients with breast cancer

Department of Medicine, Faculty of Medicine, Kuwait University, Safat, Kuwait.
The Indian Journal of Medical Research (Impact Factor: 1.4). 04/2012; 135(4):500-5.
Source: PubMed


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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    • "(Figure 7). After excluding 7 articles [19,23,30–33,35] which were the key contributors to between-study heterogeneity, the SMD of high adiponectin level was associated with decreased breast cancer risk (I2=54.6%, SMD = -0.348, "
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    ABSTRACT: Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773-1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744-0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.
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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.
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