Observational studyPLoS medicine2021
The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium.
Observational study in PLoS medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Pre-diagnostic circulating untargeted metabolomics and risk of overall and clinically significant prostate cancer: a systematic review and meta-analysis.British journal of cancer · 2026Pooled it
- The current use of proteomics and metabolomics in glomerulonephritis: a systematic literature review.Journal of nephrology · 2024Pooled it
- The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.Frontiers in oncology · 2022Pooled it
- Adiposity and cancer: epidemiology, mechanisms and future perspectives.Nature metabolism · 2026Review
- Cross-population metabolome-wide Mendelian randomization study of prostate cancer risk.Research square · 2026Article
- Adiposity, metabolites and endometrial cancer risk: inference from combinations of Mendelian randomization and observational analyses.BMC cancer · 2025Observational
- The Estonian Biobank's journey from biobanking to personalized medicine.Nature communications · 2025Review
- Urinary metabolites in association with kidney cancer risk.Carcinogenesis · 2025Article
- Identifying Metabolomic Mediators of the Physical Activity and Colorectal Cancer Relationship.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxPbioRxiv : the preprint server for biology · 2024Article
- 24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study.The American journal of clinical nutrition · 2024Article
- HCMMD: systematic evaluation of metabolites in body fluids as liquid biopsy biomarker for human cancers.Aging · 2024Review
- Data Resource Profile: The HUNT Biobank.International journal of epidemiology · 2024Article
- Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring.Frontiers in oncology · 2024Review
- Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis.Frontiers in genetics · 2024Article
- Update on Adipose Tissue and Cancer.Endocrine reviews · 2023Article
- MetaboVariation: Exploring Individual Variation in Metabolite Levels.Metabolites · 2023Article
- Article
- Metabolomic Analysis of Renal Cell Carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.Metabolites · 2022Article
- Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.BMC medicine · 2022Article
Corrections and comments
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Authors and funding
40 authors at 19 institutions in 13 countries.
Funding
Abstract
backgroundExcess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). METHODS AND
findingsWe assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.
conclusionsThis study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer.
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