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@article{Guida:2021:10.1371/journal.pmed.1003786,
author = {Guida, F and Tan, VY and Corbin, LJ and Smith-Byrne, K and Alcala, K and Langenberg, C and Stewart, ID and Butterworth, AS and Surendran, P and Achaintre, D and Adamski, J and Amiano, Exezarreta P and Bergmann, MM and Bull, CJ and Dahm, CC and Gicquiau, A and Giles, GG and Gunter, MJ and Haller, T and Langhammer, A and Larose, TL and Ljungberg, B and Metspalu, A and Milne, RL and Muller, DC and Nøst, TH and Pettersen, Sørgjerd E and Prehn, C and Riboli, E and Rinaldi, S and Rothwell, JA and Scalbert, A and Schmidt, JA and Severi, G and Sieri, S and Vermeulen, R and Vincent, EE and Waldenberger, M and Timpson, NJ and Johansson, M},
doi = {10.1371/journal.pmed.1003786},
journal = {PLoS Medicine},
title = {The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium},
url = {http://dx.doi.org/10.1371/journal.pmed.1003786},
volume = {18},
year = {2021}
}

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TY  - JOUR
AB  - 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 (&sz
AU  - Guida,F
AU  - Tan,VY
AU  - Corbin,LJ
AU  - Smith-Byrne,K
AU  - Alcala,K
AU  - Langenberg,C
AU  - Stewart,ID
AU  - Butterworth,AS
AU  - Surendran,P
AU  - Achaintre,D
AU  - Adamski,J
AU  - Amiano,Exezarreta P
AU  - Bergmann,MM
AU  - Bull,CJ
AU  - Dahm,CC
AU  - Gicquiau,A
AU  - Giles,GG
AU  - Gunter,MJ
AU  - Haller,T
AU  - Langhammer,A
AU  - Larose,TL
AU  - Ljungberg,B
AU  - Metspalu,A
AU  - Milne,RL
AU  - Muller,DC
AU  - Nøst,TH
AU  - Pettersen,Sørgjerd E
AU  - Prehn,C
AU  - Riboli,E
AU  - Rinaldi,S
AU  - Rothwell,JA
AU  - Scalbert,A
AU  - Schmidt,JA
AU  - Severi,G
AU  - Sieri,S
AU  - Vermeulen,R
AU  - Vincent,EE
AU  - Waldenberger,M
AU  - Timpson,NJ
AU  - Johansson,M
DO  - 10.1371/journal.pmed.1003786
PY  - 2021///
SN  - 1549-1277
TI  - The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
T2  - PLoS Medicine
UR  - http://dx.doi.org/10.1371/journal.pmed.1003786
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34543281
UR  - http://hdl.handle.net/10044/1/92126
VL  - 18
ER  -

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