Lifetime Body Weight Trajectories and Risk of Kidney Cancer: A Large US Prospective Cohort Study

Purpose: This study aimed to investigate kidney cancer risk in relation to the body mass index (BMI) trajectory and cumulative exposure to excess weight. Methods: We identified several anthropometric metrics to capture the lifetime BMI patterns from the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. These measures included BMI at specific ages (age 20 years, 50 years, and age at completing the baseline questionnaire), BMI trajectory from age 20 to baseline, cumulative exposure to overweight/obesity from age 20 to baseline, and weight change during each age span. The BMI trajectory was identified using the latent class trajectory model. The cumulative exposure, which was quantified by weighted years of living with overweight/obesity (WYO), was obtained by summing up the excess BMI (BMI-25, set to 0 when BMI < 25) across ages. Cox proportional hazards regression, adjusting for age, sex, randomization arm, race, education, smoking, aspirin use, history of hypertension and diabetes, was conducted to quantify the hazard ratio (HR) and 95% confidence interval (CI) for the association between each anthropometric metric and incident kidney cancer. Results: During a median follow-up of 11.5 years, incident kidney cancers were diagnosed in 391 men and 223 women. A higher BMI at age 20, 50, and baseline was associated with a greater hazard of kidney cancer. Compared to individuals who retained normal BMI throughout adulthood, an increased hazard of kidney cancer was observed for individuals who progressed from normal BMI to overweight (HR: 1.41, 95% CI: 1.15,1.73), from normal BMI to obesity (HR: 2.02, 95% CI: 1.57, 2.58), and from overweight to obesity (HR: 2.79, 95% CI: 1.88,4.13). Compared to individuals who were never overweight (WYO = 0), elevated HRs were observed among individuals who experienced low (HR: 1.22, 95% CI: 0.94, 1.57), medium (HR: 1.46, 95% CI: 1.15,1.87), and high (HR: 1.92, 95% CI: 1.51, 2.43) level of WYO (tertiles of WYO above 0). Weight gain of ≥10 kg was positively associated with kidney cancer incidence for each age span. Conclusions: Being overweight in early adulthood, weight gain in later life, and higher cumulative exposure to excess weight over the lifespan were all associated with increased risk of kidney cancer.