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Serum Adiponectin Concentrations and Tissue Expression of Adiponectin Receptors Are Reduced in Patients with Prostate Cancer: A Case Control Study

¹ Laiko University Hospital; ² Department of Pathology, University of Athens Medical School, Athens, Greece; and ³ Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Christos S. Mantzoros, Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Stoneman 816, Boston, MA 02215. Phone: 617-667-8630; Fax: 617-667-8634. E-mail: cmantzor{at}bidmc.harvard.edu

Purpose: Adiponectin, an adipocyte-secreted hormone with insulin-sensitizing effects, has been inversely associated with several hormonally dependent malignancies, including breast, endometrial, and colorectal cancer. Few studies have examined serum adiponectin in relation to prostate cancer, and expression of adiponectin receptors has previously not been assessed in prostate tumors.

Experimental Design: We collected plasma samples and covariate data in the context of a case-control study of 300 Greek men, including 75 prostate cancer cases, 75 patients with benign prostatic hyperplasia (BPH), and 150 healthy controls. Prostate tissue samples were taken from 72 cases and 27 noncases and examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry.

Results: Prostate cancer patients had significantly lower plasma adiponectin concentrations as compared with men with BPH and healthy controls (7.4 ± 5.0 versus 11.5 ± 6.4 and 12.8 ± 8.0 ng/mL, respectively). Men in the top two quartiles of adiponectin had a 71% to 73% reduced risk of prostate cancer as compared with men in the lowest quartile after adjusting for age, body mass index, and additional potential confounders. We found no similar relationship between adiponectin and risk of BPH. Results from immunohistochemistry experiments show weaker expression of adiponectin receptors AdipoR1 and AdipoR2 in cancerous versus healthy prostate tissue.

Conclusions: Higher serum adiponectin is associated with a marked reduction in risk of prostate cancer, but not BPH, independently of other risk factors. Malignant prostate tissue samples have reduced expression of adiponectin receptors as compared with benign prostate tissue. These results support a role for adiponectin in the pathogenesis of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(2):308–13)

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