TY - JOUR
T1 - Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
AU - Clasen, Joanna L.
AU - Heath, Alicia K.
AU - Van Puyvelde, Heleen
AU - Huybrechts, Inge
AU - Park, Jin Young
AU - Ferrari, Pietro
AU - Scelo, Ghislaine
AU - Ulvik, Arve
AU - Midttun, Øivind
AU - Ueland, Per Magne
AU - Overvad, Kim
AU - Eriksen, Anne Kirstine
AU - Tjønneland, Anne
AU - Kaaks, Rudolf
AU - Katzke, Verena
AU - Schulze, Matthias B.
AU - Palli, Domenico
AU - Agnoli, Claudia
AU - Chiodini, Paolo
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Zamora-Ros, Raul
AU - Rodriguez-Barranco, Miguel
AU - Santiuste, Carmen
AU - Ardanaz, Eva
AU - Amiano, Pilar
AU - Schmidt, Julie A.
AU - Weiderpass, Elisabete
AU - Gunter, Marc
AU - Riboli, Elio
AU - Cross, Amanda J.
AU - Johansson, Mattias
AU - Muller, David C.
N1 - Publisher Copyright:
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - 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.
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.
KW - dietary biomarkers
KW - kidney cancer
KW - transsulfuration
KW - vitamin B6
UR - http://www.scopus.com/inward/record.url?scp=85128755062&partnerID=8YFLogxK
U2 - 10.1002/ijc.34009
DO - 10.1002/ijc.34009
M3 - Article
SN - 0020-7136
VL - 151
SP - 708
EP - 716
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -