Leptin is associated with increased prostate cancer risk: A nested case-referent study

A Western lifestyle has been implicated in the pathogenesis of prostate can cer. However, no clear association between obesity and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and rece ptors for leptin are present in the prostate. Leptin may, thus, be associat ed with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in No rthern Sweden. Blood pressure, body mass index, and use of tobacco were rec orded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and sex hormone-binding globulin were analyzed in stored samples. Their influences on prostate cancer were estimated by c onditional logistic regression analysis. Prostate cancer specimens were inv estigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of le ptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.1), and 1.6 (0.8-3. 2). Adjustments for metabolic variables, testosterone, and IGF-I and its bi nding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepith elial neoplasia lesions and malignant prostatic epithelium. Moderately elev ated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic i ntraepithelial neoplasia lesions, or to indirect actions through other mech anisms. A critical fat mass related to an interior milieu favorable for pro state cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.