Aarhus Universitets segl

Julie Schmidt

Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

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  • Joanna L Clasen, Imperial College London, Storbritannien
  • Alicia K Heath, Imperial College London, Storbritannien
  • Heleen Van Puyvelde, World Health Organization, Ghent University, Frankrig
  • Inge Huybrechts, World Health Organization, Frankrig
  • Jin Young Park, World Health Organization, Frankrig
  • Pietro Ferrari, World Health Organization, Frankrig
  • Ghislaine Scelo, University of Turin, Italien
  • Arve Ulvik, Bevital AS, Norge
  • Øivind Midttun, Bevital AS
  • ,
  • Per Magne Ueland, Bevital AS
  • ,
  • Kim Overvad
  • Anne Kirstine Eriksen, Kræftens Bekæmpelse, Danmark
  • Anne Tjønneland, Kræftens Bekæmpelse, Danmark
  • Rudolf Kaaks, German Cancer Research Center, Tyskland
  • Verena Katzke, German Cancer Research Center, Tyskland
  • Matthias B Schulze, German Institute of Human Nutrition Potsdam-Rehbruecke, University of Potsdam, Tyskland
  • Domenico Palli, Institute for the Study and Prevention of Cancer (ISPRO), Italien
  • Claudia Agnoli, IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano, Italien
  • Paolo Chiodini, Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Italien
  • Rosario Tumino, Hyblean Association for Epidemiological Research (AIRE-ONLUS), Italien
  • Carlotta Sacerdote, Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino, Italien
  • Raul Zamora-Ros, Bellvitge Biomedical Research Institute - IDIBELL, Spanien
  • Miguel Rodriguez-Barranco, Escuela Andaluza de Salud Publica, University of Granada, CIBER - Center for Biomedical Research Network, Spanien
  • Carmen Santiuste, CIBER - Center for Biomedical Research Network, Murcia Regional Health Council, Spanien
  • Eva Ardanaz, CIBER - Center for Biomedical Research Network, Universidad Pública de Navarra, Navarra Institute for Health Research (IdiSNA), Spanien
  • Pilar Amiano, CIBER - Center for Biomedical Research Network, Ministry of Health of the Basque Government, Instituto de Investigación Sanitaria Biodonostia, Spanien
  • Julie A Schmidt
  • Elisabete Weiderpass, World Health Organization, Frankrig
  • Marc Gunter, World Health Organization
  • ,
  • Elio Riboli, Imperial College London, Storbritannien
  • Amanda J Cross, Imperial College London, Storbritannien
  • Mattias Johansson, World Health Organization, Frankrig
  • David C Muller, Imperial College London, Storbritannien

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.

TidsskriftInternational Journal of Cancer
Sider (fra-til)708-716
Antal sider9
StatusUdgivet - sep. 2022

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