Obesity and renal cell carcinoma risk by histologic subtype: A nested case-control study and meta-analysis

Background: Although obesity is an established risk factor for renal cell carcinoma (RCC), it is unclear whether this relationship varies across histologic subtypes. Methods: We conducted a nested case-control study within the Kaiser Permanente Northern California (KPNC) health care network, and meta-analysis combining our results with those of previously published studies. Our KPNC study included 685 RCC cases [421 clear cell; 65 papillary; 24 chromophobe; 35 other; 141 not otherwise specified (NOS)] and 4266 controls. Subtype-specific odds ratios (ORs) and 95% confidence intervals (CIs) for categories of body mass index (BMI) and were computed from the case-control data using polytomous logistic regression. Findings from this and other relevant studies were combined by meta-analysis using a random effects model. Results: In the KPNC study, obesity (BMI ≥ 30 kg/m ² ) was associated with clear cell RCC (OR 1.5, 95% CI 1.1–2.1) and chromophobe RCC (OR 2.5, 95%CI 0.8–8.1), but not with papillary RCC (OR 1.0, 95% CI 0.5–1.9). In meta-analysis including three additional studies, a similar pattern of summary relative risks (SRR) for obesity was observed across subtypes (clear cell: SRR 1.8, 95% CI 1.5–2.2; chromophobe: SRR 2.2, 95% CI 1.3–3.7; papillary, SRR 1.2, 95% CI 0.8–1.6). Conclusions: These findings support the hypothesis that histologic subtypes of RCC possess distinct etiologic pathways, with obesity important for the development of clear cell and, possibly, chromophobe RCC, but not papillary RCC.