biostudies-literatureAlcala KUmeå UniversitetWorld Cancer Research FundCancer Research UKBengt Ihres FoundationSvenska LäkaresällskapetMedical Research CouncilNational Institute for Health Research (NIHR)National Institute for Health and Care ResearchSvensk-Franska StiftelsenNIHR Bristol Biomedical Research Centree1004906https://www.ebi.ac.uk/biostudies/studies/S-EPMC12919923biostudies-literatureUnknown23(2)<h4>Background</h4>Excess body adiposity is an established cause of renal cancer, but underlying molecular pathways mediating this relationship remain unclear. This study aimed to systematically evaluate a panel of obesity-related risk factors as potential mediators in renal cancer etiology.<h4>Methods and findings</h4>We used two complementary approaches to evaluate obesity-related risk factors in renal cancer etiology: (i) direct risk factor assessment in longitudinal cohorts and (ii) genetically proxied risk factors through two-sample mendelian randomization (MR). Direct risk-factor association-analyses (i.e., cohort analyses) were based on the UK Biobank cohort study (472,337 cohort participants, including 1,382 incident renal cancer cases diagnosed during 5,586,414 person years of folPLoS medicineSystematic assessment of obesity-related risk factors in renal cancer etiology: A longitudinal risk and mendelian randomization analysis.PMC12919923F0025_230413NIHR202411IIG_2019_1995FS 2.1.6-59-23C18281/A29019MC_UU_00032/1SLS-960379BRC-1215-20011PRCPGM-May25/100001Brennan PFranklin OPollak MAlcala KLangdon RJacobson SSmith GDDimou NMariosa DMartin RMJohansson MGunter MJCoscia-Requena CfalseSystematic assessment of obesity-related risk factors in renal cancer etiology: A longitudinal risk and mendelian randomization analysis.<h4>Background</h4>Excess body adiposity is an established cause of renal cancer, but underlying molecular pathways mediating this relationship remain unclear. This study aimed to systematically evaluate a panel of obesity-related risk factors as potential mediators in renal cancer etiology.<h4>Methods and findings</h4>We used two complementary approaches to evaluate obesity-related risk factors in renal cancer etiology: (i) direct risk factor assessment in longitudinal cohorts and (ii) genetically proxied risk factors through two-sample mendelian randomization (MR). Direct risk-factor association-analyses (i.e., cohort analyses) were based on the UK Biobank cohort study (472,337 cohort participants, including 1,382 incident renal cancer cases diagnosed during 5,586,414 person years of fol2026-01-01T00:00:00Z2026 Feb2026-07-16T10:01:36.958Z2026-07-09T10:48:07.929ZS-EPMC129199234166623110.1371/journal.pmed.1004906