GlaxoSmithKline R&D, Worldwide Epidemiology (Oncology), Collegeville, PA, USA.
Clin Chem. 2010 Jan;56(1):34-43. doi: 10.1373/clinchem.2009.133272. Epub 2009 Nov 12.
Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes.
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.
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; P(trend) = 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; P(trend) = 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 >or=25 kg/m(2) (HR(Q5 vs Q1)= 0.10; 95% CI 0.01-0.78; P(trend) = 0.02), but not among men of normal weight (P(trend) = 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.
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.
脂肪细胞因子可能介导肥胖与致命性前列腺癌结局之间的关联。
在医师健康研究中，我们前瞻性地研究了诊断前血浆脂联素和瘦素浓度与发生前列腺癌（1982-2000 年诊断的 654 例病例和 644 例年龄匹配的对照者）的风险之间的关系，以及在病例中，到 2007 年死于前列腺癌的风险。
脂联素浓度与总体前列腺癌风险无关。然而，脂联素浓度较高的男性患高级别或致命性癌症（转移性或致命性疾病）的风险较低。与最低五分位数相比，最高五分位数的相对风险（95%可信区间）为 0.25（95%可信区间 0.07-0.87；P 趋势=0.02），用于致命性癌症。在所有病例中，较高的脂联素浓度预示着前列腺癌特异性死亡率较低[风险比（HR）（Q5 与 Q1）=0.39；95%可信区间 0.17-0.85；P 趋势=0.02]，独立于体重指数（BMI）、血浆 C 肽（胰岛素分泌的标志物）、瘦素、临床分期和肿瘤分级。这种反比关系主要见于 BMI≥25kg/m2 的男性（HR（Q5 与 Q1）=0.10；95%可信区间 0.01-0.78；P 趋势=0.02），而不是体重正常的男性（P 趋势=0.51）。尽管瘦素浓度与 BMI 的相关性（r=0.58，P<0.001）强于脂联素（r=-0.17，P<0.001），但瘦素与前列腺癌风险或死亡率无关。
较高的诊断前脂联素（而非瘦素）浓度使男性更易发生高级别前列腺癌，并且随后死于癌症的风险降低，提示肥胖与不良前列腺癌结局之间存在机制联系。
