Lifetime body weight patterns, weight loss, and renal cell carcinoma subtypes

Background: Increased body mass index (BMI) in midlife is a recognized risk factor for renal cell carcinoma (RCC), but data on lifetime BMI patterns and their associations with RCC and subtypes remain limited. Methods: In the National Institutes of Health–American Association of Retired Persons Diet and Health Study (n = 204,364), the authors evaluated lifetime body weight patterns using: 1) BMI at ages 18, 35, 50, and baseline (mean [SD]: 61.6 [5.3] years); 2) BMI trajectory across adulthood; 3) cumulative exposure to excess weight, measured as weighted years overweight/obese (WYO); and 4) BMI change between specific ages. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall RCC (n = 1425), aggressive RCC (n = 583), fatal RCC (n = 339), and histologic subtypes, including clear cell RCC (ccRCC, n = 541), papillary RCC (pRCC, n = 146), and chromophobe RCC (chRCC, n = 64). Results: Higher BMI at all ages was associated with greater hazard of overall RCC and all subtypes (HR, 1.10–1.40 per 5-unit increase), except chRCC (HR, 0.80–0.98). Similar patterns were observed for BMI trajectories indicating weight gain during adulthood to overweight/obesity, compared to maintaining normal BMI. Higher WYO (per SD increase) was associated with an elevated hazard of overall RCC (HR, 1.17; 95% CI, 1.12–2.22), aggressive RCC (HR, 1.21; 95% CI, 1.13–1.29), fatal RCC (HR, 1.16; 95% CI, 1.06–1.27), and ccRCC (HR, 1.20; 95% CI, 1.13–1.30), but not pRCC (HR, 1.13; 95% CI, 0.97–1.32) and chRCC (HR, 0.92; 95% CI, 0.68–1.25). BMI reduction of ≥10%, particularly after age 50 (HR, 0.72; 95% CI, 0.52–0.99), was associated with lower RCC hazard. Conclusions: Lifetime excess weight and adult weight gain were associated with increased risk of RCC, particularly ccRCC, whereas weight loss was associated with reduced risk.