Circulating levels of obesity-related markers and risk of renal cell carcinoma in the PLCO cancer screening trial

Purpose: Obesity is an established risk factor for renal cell carcinoma (RCC). It is unclear what biologic mechanisms underlie this association, although recent evidence suggests that the effects of circulating hormones such as insulin-like growth factors (IGF) and adipokines may play a role. Methods: To address this question, we conducted a nested case–control study of RCC (252 cases, 252 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial investigating associations with pre-diagnostic serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, IGF-1, IGF-binding protein-3 (IGFBP-3), and C-peptide. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic regression. Results: After adjustment for potential confounders, non-significant associations with RCC were observed for total adiponectin (OR for highest vs. lowest quartile = 0.65, 95% CI 0.37–1.14; p_trend = 0.35), HMW adiponectin (0.67, 0.38–1.17; p_trend = 0.36), IGF-1 (1.35, 0.77–2.39; p_trend = 0.17), IGFBP-3 (1.47, 0.83–2.62; p_trend = 0.53), and C-peptide (1.52, 0.86–2.70; p_trend = 0.15). In a joint analysis with body mass index (BMI, kg/m²), obese individuals (BMI ≥30) with above-median levels of IGFBP-3 had a significantly higher risk versus those with BMI <25 and below-median IGFBP-3 (OR 2.42, 1.11–5.26), whereas obese individuals with low IGFBP-3 did not (1.18, 0.53–2.64) (p_interaction = 0.35). Conclusions: The results of this study, while not clearly supporting associations with these obesity-related hormones, suggest that the association between obesity and RCC may be partially modified through mechanisms related to elevated IGFBP-3.