A 25-Year Prospective Study of Plasma Adiponectin and Leptin Concentrations and Prostate Cancer Risk and Survival

Abstract

Background: Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes. Methods: In the Physicians’ Health Study, we prospectively examined the association of prediagnostic plasma concentrations of adiponectin and leptin with risk of developing incident prostate cancer (654 cases diagnosed 1982–2000 and 644 age-matched controls) and, among cases, risk of dying from prostate cancer by 2007. Results: Adiponectin concentrations were not associated with risk of overall prostate cancer. However, men with higher adiponectin concentrations had lower risk of developing high-grade or lethal cancer (metastatic or fatal disease). The relative risk (95% CI) comparing the highest quintile to the lowest (Q5 vs Q1) was 0.25 (95% CI 0.07–0.87; Ptrend = 0.02) for lethal cancer. Among all the cases, higher adiponectin concentrations predicted lower prostate cancer–specific mortality [hazard ratio (HR)Q5 vs Q1= 0.39; 95% CI 0.17–0.85; Ptrend = 0.02], independent of body mass index (BMI), plasma C-peptide (a marker of insulin secretion), leptin, clinical stage, and tumor grade. This inverse association was apparent mainly among men with a BMI ≥25 kg/m2 (HRQ5 vs Q1= 0.10; 95% CI 0.01–0.78; Ptrend = 0.02), but not among men of normal weight (Ptrend = 0.51). Although the correlation of leptin concentrations with BMI (r = 0.58, P < 0.001) was stronger than that of adiponectin (r = −0.17, P < 0.001), leptin was unrelated to prostate cancer risk or mortality. Conclusions: Higher prediagnostic adiponectin (but not leptin) concentrations predispose men to a lower risk of developing high-grade prostate cancer and a lower risk of subsequently dying from the cancer, suggesting a mechanistic link between obesity and poor prostate cancer outcome.