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.This article is protected by copyright. All rights reserved.
About The Expert
Joanna L Clasen
Alicia K Heath
Heleen Van Puyvelde
Inge Huybrechts
Jin Young Park
Pietro Ferrari
Ghislaine Scelo
Arve Ulvik
Øivind Midttun
Per Magne Ueland
Kim Overvad
Anne Kirstine Eriksen
Anne Tjønneland
Rudolf Kaaks
Verena Katzke
Matthias B Schulze
Domenico Palli
Claudia Agnoli
Paolo Chiodini
Rosario Tumino
Carlotta Sacerdote
Raul Zamora-Ros
Miguel Rodriguez-Barranco
Carmen Santiuste
Eva Ardanaz
Pilar Amiano
Julie A Schmidt
Elisabete Weiderpass
Marc Gunter
Elio Riboli
Amanda J Cross
Mattias Johansson
David C Muller
References
PubMed