Despite a well-established link between
obesity and
renal cell carcinoma (RCC), the mechanism through which
obesity acts to increase
cancer risk is unclear.
Adiponectin,
leptin and
resistin are adipocyte-secreted
peptide hormones that may influence RCC development through their demonstrated effects on
inflammation,
insulin resistance and cell growth and proliferation. We conducted a nested case-control study to evaluate whether prediagnostic serum
adiponectin,
leptin and
resistin levels are associated with RCC risk. This case-control study (273 cases and 273 controls) was nested within the
Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study cohort of Finnish male smokers. Odds ratios (
ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic regression models, with analyte levels modeled continuously and categorically (defined using quartiles among controls). High
adiponectin levels were significantly associated with reduced RCC risk (Quartile 4 versus Quartile 1: OR = 0.52, 95% CI = 0.30-0.88; P trend = 0.01). This association remained upon additional adjustment for body mass index at blood collection and exclusion of cases diagnosed within the first 2 years of follow-up. In addition, model adjustment for
adiponectin resulted in a substantial attenuation of the association between BMI and RCC (OR per 5 kg/m(2) changed from 1.19 to 1.05). No clear associations with RCC were observed for
leptin or
resistin. Our results suggest that elevated levels of circulating
adiponectin are associated with decreased subsequent risk of RCC. These findings provide the strongest evidence to date, suggesting that the association between
obesity and RCC is mediated at least in part through the effects of low
adiponectin.