| Summary: | This study includes 3 main analytical steps: (i) the investigation of the associations between circulating levels of metabolites and kidney cancer risk using pre-diagnostic measurements in a case–control study nested within multiple large-scale prospective cohorts; (ii) the assessment of the causal effect of BMI, the leading modifiable risk factor for kidney cancer, on circulating metabolites levels; and (iii) the evaluation of the overlap between the metabolic footprint of BMI and that of kidney cancer risk. The orange X’s indicate the time at which a participant is diagnosed with kidney cancer when his follow-up is stopped. Controls have been selected among participants free of cancer at the time their matched case was diagnosed. Metabolites from all samples have been measured on the Biocrates platform, while only samples from EPIC and NSHDS cohorts have been measured with Metabolon platform. BMI, body mass index; EPIC, The European Prospective Investigation into Cancer and Nutrition; Estonian BB, University of Tartu—Estonian Biobank; HUNT, The Trøndelag Health Study; LC–MS, liquid chromatography–tandem mass spectrometry; MCCS, The Melbourne Collaborative Cohort Study; MR, mendelian randomisation; NSHDS, Northern Sweden Health and Disease study; SNP, single nucleotide polymorphism.
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