RT Journal Article
T1 Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
A1 Clasen, Joanna L
A1 Heath, Alicia K
A1 Van Puyvelde, Heleen
A1 Huybrechts, Inge
A1 Park, Jin Young
A1 Ferrari, Pietro
A1 Scelo, Ghislaine
A1 Ulvik, Arve
A1 Midttun, Øivind
A1 Ueland, Per Magne
A1 Overvad, Kim
A1 Eriksen, Anne Kirstine
A1 Tjønneland, Anne
A1 Kaaks, Rudolf
A1 Katzke, Verena
A1 Schulze, Matthias B
A1 Palli, Domenico
A1 Agnoli, Claudia
A1 Chiodini, Paolo
A1 Tumino, Rosario
A1 Sacerdote, Carlotta
A1 Zamora-Ros, Raul
A1 Rodriguez-Barranco, Miguel
A1 Santiuste, Carmen
A1 Ardanaz, Eva
A1 Amiano, Pilar
A1 Schmidt, Julie A
A1 Weiderpass, Elisabete
A1 Gunter, Marc
A1 Riboli, Elio
A1 Cross, Amanda J
A1 Johansson, Mattias
A1 Muller, David C
K1 dietary biomarkers
K1 kidney cancer
K1 transsulfuration
K1 vitamin B6
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 associations 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 to 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.
PB John Wiley & Sons, Inc.
YR 2022
FD 2022-03-02
LK http://hdl.handle.net/10668/22073
UL http://hdl.handle.net/10668/22073
LA en
NO Clasen JL, Heath AK, Van Puyvelde H, Huybrechts I, Park JY, Ferrari P, et al. Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Int J Cancer. 2022 Sep 1;151(5):708-716.
NO This work was supported by the Imperial CollegeLondon President's PhD Scholarship to JoannaL. Clasen; the Cancer Research UK PopulationResearch Fellowship to David C. Muller; WorldCancer Research Fund (grant number2013/1005) to Pietro Ferrari; and biomarkerlaboratory analysis was funded by World CancerResearch Fund (grant number 2010/254). Thecoordination of EPIC is financially supported byInternational Agency for Research on Cancer(IARC) and also by the Department ofEpidemiology and Biostatistics, School of PublicHealth, Imperial College London which hasadditional infrastructure support provided by theNIHR Imperial Biomedical Research Centre (BRC).The national cohorts are supported by: DanishCancer Society (Denmark); Ligue Contre le Cancer,Institut Gustave Roussy, Mutuelle Générale del'Education Nationale, Institut National de la Santéet de la Recherche Médicale (INSERM) (France);German Cancer Aid, German Cancer ResearchCenter (DKFZ), German Institute of HumanNutrition Potsdam-Rehbruecke (DIfE), FederalMinistry of Education and Research (BMBF)(Germany); Associazione Italiana per la Ricerca sulCancro-AIRC-Italy, Compagnia di SanPaolo andNational Research Council (Italy); Dutch Ministryof Public Health, Welfare and Sports (VWS),Netherlands Cancer Registry (NKR), LK ResearchFunds, Dutch Prevention Funds, Dutch ZON (ZorgOnderzoek Nederland), World Cancer ResearchFund (WCRF), Statistics Netherlands (TheNetherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), RegionalGovernments of Andalucía, Asturias, BasqueCountry, Murcia and Navarra, and the CatalanInstitute of Oncology—ICO (Spain); SwedishCancer Society, Swedish Research Council andCounty Councils of Skåne and Västerbotten(Sweden); Cancer Research UK (14136 to EPICNorfolk; C8221/A29017 to EPIC-Oxford), MedicalResearch Council (1000143 to EPIC-Norfolk;MR/M012190/1 to EPIC-Oxford)(United Kingdom). We also thank CERCAProgram/Generalitat de Catalunya for theinstitutional support to IDIBELL. Raul Zamora-Roswould like to thank the “Miguel Servet” program(CPII20/00009) from the Institute of Health CarlosIII (Spain) and the European Social Fund (ESF).
DS RISalud
RD Apr 17, 2025