A prospective study of plasma adiponectin levels and prostate cancer risk and survival.

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A prospective study of plasma adiponectin levels and prostate cancer risk and survival ABSTRACT Background: Obesity/Overweight is associated with metastatic and fatal prostate cancer and predicts poor survival; it thus may play a significant role in cancer progression. Adiponectin is an adipocyte-derived cytokine, and its circulating levels are inversely correlated with adiposity. At physiological concentrations, adiponectin inhibits in vitro cell growth of both the androgen-dependent and androgen-independent prostate cancer cell lines, and might therefore be beneficial. However, human data is very sparse. Methods: In the Physicians' Health Study, after excluding men who reported diabetes at the baseline, 610 cases and 583 age-matched controls were available for the analyses. We examined the associations of prediagnostic plasma adiponectin levels with prostate cancer incidence among 583 case-control pairs (1:1), using conditional logistic regression. Of these cases, 194 men had high-grade (Gleason 7-10 or poorly differentiated) tumor and 117 men had lethal disease, defined as stage D at diagnosis, or developed metastases or died of prostate cancer during the follow-up by 2005. We further applied Cox proportional hazards models to assess the role of adiponectin in prostate cancer survival among 610 cases. Results: Adiponectin levels were inversely correlated with baseline body mass index (BMI, correlation coefficient, r = -0.18, P <0.001), and the means (standard deviations) were 24.1 (2.5) kg/m² for quintile 5 and 25.2 (2.3) kg/m² for quintile 1. Men with higher plasma adiponectin levels had lower baseline prostate-specific antigen (PSA) levels (P = 0.02) and were less likely to develop lethal prostate cancer after diagnosis (P = 0.01). Higher adiponectin level at baseline (quintile 5 versus 1) was associated with significantly reduced risks of total (odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.45-0.99; P_trend = 0.20), high-grade (OR = 0.44, 95% CI 0.21-0.92; P_trend = 0.18), in particular, lethal prostate cancer (OR = 0.19, 95% CI 0.06-0.65, P_trend = 0.02) and better survival (hazard ratio [HR] = 0.43, 95% CI 0.19-0.95, P_trend = 0.03). These associations were independent of BMI, C-peptide, and the major components of the insulin-like growth factor system. Conclusions: Adiponectin may contribute to the pathogenesis of prostate cancer and predict prostate cancer prognosis.