ABSTRACT: OBJECTIVE:The incidence of renal cell carcinoma (RCC) has increased rapidly in the U.S., particularly among African Americans. Despite a well-established link between obesity and RCC, the mechanism through which obesity increases cancer risk has yet to be established. Adipokines, such as leptin and adiponectin, may link obesity and cancer, with different quantitative effects by race. DESIGN AND METHODS:We evaluated the association between leptin and adiponectin concentrations and RCC risk among Caucasians (581 cases, 558 controls) and African Americans (187 cases, 359 controls) in a case-control study conducted in Detroit and Chicago. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated using unconditional logistic regression. RESULTS:Among controls, Caucasians had higher median adiponectin than African Americans (males: 8.2 vs. 7.0 ?g/ml, P = 0.001; females: 13.4 vs. 8.4 ?g/ml, P < 0.0001), and lower median leptin than African Americans (males: 11.8 vs. 14.1 ng/ml, P = 0.04; females: 28.3 vs. 45.9 ng/ml, P < 0.0001). Among Caucasians, the ORs for RCC comparing the highest (Q4) to the lowest (Q1) sex-specific quartile of leptin were 3.2 (95% CI: 1.9-5.2) for males and 4.7 (95% CI: 2.6-8.6) for females. Serum leptin was not significantly associated with RCC among African American males (OR 1.5, 95% CI: 0.7-3.1) or females (OR 2.1, 95% CI: 0.8-5.5). Higher adiponectin was associated with RCC risk among African American males (Q4 vs. Q1: OR 2.3, 95% CI: 1.1-4.6) and females (OR 2.1, 95% CI: 1.2-6.7), but not significantly among Caucasian males (OR 1.6, 95% CI: 0.99-2.7) and females (OR 1.6, 95% CI: 0.9-3.1). CONCLUSION:We observed an association between both leptin and adiponectin concentrations and risk of RCC, which may differ by race. Confirmation in further investigations is needed.