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@article{Clasen:2022:10.1002/ijc.34009,
author = {Clasen, JL and Heath, AK and Van, Puyvelde H and Huybrechts, I and Park, JY and Ferrari, P and Scelo, G and Ulvik, A and Midttun, Ø and Ueland, PM and Overvad, K and Eriksen, AK and Tjønneland, A and Kaaks, R and Katzke, V and Schulze, MB and Palli, D and Agnoli, C and Chiodini, P and Tumino, R and Sacerdote, C and Zamora-Ros, R and Rodriguez-Barranco, M and Santiuste, C and Ardanaz, E and Amiano, P and Schmidt, JA and Weiderpass, E and Gunter, M and Riboli, E and Cross, AJ and Johansson, M and Muller, DC},
doi = {10.1002/ijc.34009},
journal = {International Journal of Cancer},
pages = {708--716},
title = {Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study},
url = {http://dx.doi.org/10.1002/ijc.34009},
volume = {151},
year = {2022}
}

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TY  - JOUR
AB  - Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved.
AU  - Clasen,JL
AU  - Heath,AK
AU  - Van,Puyvelde H
AU  - Huybrechts,I
AU  - Park,JY
AU  - Ferrari,P
AU  - Scelo,G
AU  - Ulvik,A
AU  - Midttun,Ø
AU  - Ueland,PM
AU  - Overvad,K
AU  - Eriksen,AK
AU  - Tjønneland,A
AU  - Kaaks,R
AU  - Katzke,V
AU  - Schulze,MB
AU  - Palli,D
AU  - Agnoli,C
AU  - Chiodini,P
AU  - Tumino,R
AU  - Sacerdote,C
AU  - Zamora-Ros,R
AU  - Rodriguez-Barranco,M
AU  - Santiuste,C
AU  - Ardanaz,E
AU  - Amiano,P
AU  - Schmidt,JA
AU  - Weiderpass,E
AU  - Gunter,M
AU  - Riboli,E
AU  - Cross,AJ
AU  - Johansson,M
AU  - Muller,DC
DO  - 10.1002/ijc.34009
EP  - 716
PY  - 2022///
SN  - 0020-7136
SP  - 708
TI  - Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
T2  - International Journal of Cancer
UR  - http://dx.doi.org/10.1002/ijc.34009
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35366005
UR  - https://onlinelibrary.wiley.com/doi/10.1002/ijc.34009
UR  - http://hdl.handle.net/10044/1/96292
VL  - 151
ER  -

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