• Stanford University School of Medicine, Palo Alto, United States.
• University of Kentucky, Lexington, KY, United States.
• Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States.
• University of California, San Francisco, San Francisco, CA, United States.
• Stanford Cancer Institute, Stanford, CA, United States.
• Stanford University School of Medicine, Stanford, CA, United States.
• Stanford University School of Medicine, Palo Alto, CA, United States.

BACKGROUND: Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess bodyweight.

METHODS: Using the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N=138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: 1) BMI at specific ages; 2) adulthood BMI trajectories; 3) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and 4) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC.

RESULTS: A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared to individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight (HR:1.49, 95%CI:1.19,1.87), from normal BMI to obesity (HR:2.22, 95%CI:1.70,2.90), and from overweight to obesity (HR:2.78, 95%CI:1.81,4.27). Compared to individuals who were never overweight (WYO=0), elevated HRs were observed among individuals who experienced low (HR:1.31, 95%CI:0.99,1.74), medium (HR:1.57, 95%CI:1.20,2.05), and high (HR:2.10, 95%CI:1.62,2.72) WYO tertile. Weight gain of ≥10kg was associated with increased RCC incidence for each age span.

CONCLUSIONS: Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk.

IMPACT: It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.