Is early-life obesity associated with kidney cancer in adulthood?-insights from genetic studies.

Abstract

Background: Adult obesity increases the risk of kidney cancer (KIC), yet the link between early body size traits and KIC remains uncertain. This study aimed to investigate the causal relationship between early body size characteristics and KIC, including its subtypes, using Mendelian randomization (MR).

Methods: We utilized data from public genome-wide association study (GWAS) databases on birth weight and body mass index (BMI) across childhood, adolescence, and adulthood as exposure variables, and KIC and its subtypes as outcome variables. A two-way two-sample MR analysis was performed to explore these associations, with the inverse variance weighted (IVW) method as the primary analytical approach and sensitivity analyses to assess result stability.

Results: IVW analysis revealed significant associations between childhood obesity [odds ratio (OR) =1.08, 95% confidence interval (CI): 1.04-1.14, P<0.001], childhood BMI (OR =1.23, 95% CI: 1.07-1.42, P=0.003), adolescent BMI (OR =1.22, 95% CI: 1.07-1.40, P=0.003), and adult BMI (OR =1.75, 95% CI: 1.41-2.17, P<0.001) with increased risk of KIC. Similar associations were observed for clear cell renal cell carcinoma (ccRCC), with childhood obesity (OR =1.09, 95% CI: 1.02-1.15, P=0.007), childhood BMI (OR =1.33, 95% CI: 1.14-1.55, P<0.001), adolescent BMI (OR =1.24, 95% CI: 1.04-1.47, P=0.01), and adult BMI (OR =1.97, 95% CI: 1.51-2.57, P<0.001) significantly linked to higher ccRCC risk. No evidence of reverse causation was found.

Conclusions: This study provides MR evidence supporting a causal association between early-life obesity and KIC. Our findings suggest that reducing obesity in early life may have a potential positive impact on the prevention of KIC.