دورية أكاديمية
The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
| العنوان: | The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium |
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| المؤلفون: | Guida, F, Tan, VY, Corbin, LJ, Smith-Byrne, K, Alcala, K, Langenberg, C, Stewart, ID, Butterworth, AS, Surendran, P, Achaintre, D, Adamski, J, Amiano Exezarreta, P, Bergmann, MM, Bull, CJ, Dahm, CC, Gicquiau, A, Giles, GG, Gunter, MJ, Haller, T, Langhammer, A, Larose, TL, Ljungberg, B, Metspalu, A, Milne, RL, Muller, DC, Nøst, TH, Pettersen Sørgjerd, E, Prehn, C, Riboli, E, Rinaldi, S, Rothwell, JA, Scalbert, A, Schmidt, JA, Severi, G, Sieri, S, Vermeulen, R, Vincent, EE, Waldenberger, M, Timpson, NJ, Johansson, M |
| المساهمون: | Cancer Research UK |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2021 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | General & Internal Medicine, 11 Medical and Health Sciences |
| جغرافية الموضوع: | United States |
| الوصف: | BACKGROUND: Excess 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 FINDINGS: We 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1549-1277 |
| العلاقة: | PLoS Medicine; http://hdl.handle.net/10044/1/92126Test; C57955/A24390; 24390 |
| DOI: | 10.1371/journal.pmed.1003786 |
| الإتاحة: | https://doi.org/10.1371/journal.pmed.1003786Test http://hdl.handle.net/10044/1/92126Test |
| حقوق: | © 2021 Guida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.641E410C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15491277 |
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| DOI: | 10.1371/journal.pmed.1003786 |