Association between weight cycling and risk of kidney cancer: a prospective cohort study and meta-analysis of observational studies

Purpose: Weight cycling is common in populations. However, it is unclear whether frequency and magnitude of weight cycling is associated with kidney cancer risk, independent of body mass index (BMI). Methods: A prospective cohort study followed 85,562 participants from Health Professionals Follow-up Study and Nurses’ Health Study (1992–2014). At baseline, participants reported frequency and magnitude of intentional weight loss in the past 4 years. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We also conducted a meta-analysis of all available observational studies including our two cohorts. Results: During 22 years of follow-up, we identified 441 kidney cancer cases. Compared with non-weight cyclers (no attempt of intentional weight loss), severe cyclers (≥ 3 times of intentional weight loss of ≥ 4.5 kg) were at increased kidney cancer risk after adjusting for BMI before weight cycling (pooled multivariable-adjusted HR, 1.78; 95% CI, 1.19, 2.66). Additional adjustment for attained BMI after weight cycling had minimal influence. There was a positive trend between weight cycling by frequency and magnitude and kidney cancer risk (P-trend = 0.01). Moreover, the observed positive association did not differ by subtypes of cyclers (e.g., adiposity status, weight-loss methods). In the meta-analysis, we found a strong positive association between weight cycling and kidney cancer risk (summary relative risk for weight cyclers vs. non-cyclers, 1.51; 95% CI, 1.16, 1.96; I²: 52.2%; 6 studies). Conclusion: Frequent substantial weight cycling was associated with increased risk of kidney cancer, independent of BMI. Our study suggests that weight cycling may be an important risk factor for kidney cancer.