One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case–control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98–1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02–1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62–10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81–1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.


  • Alina Vrieling
  • H. Bas Bueno-De-Mesquita
  • Martine M. Ros
  • Ellen Kampman
  • Katja K. Aben
  • Frederike L. Büchner
  • Eugène H. Jansen
  • Nina Roswall
  • Anne Tjønneland
  • Marie Christine Boutron-Ruault
  • Claire Cadeau
  • Jenny Chang-Claude
  • Rudolf Kaaks
  • Steffen Weikert
  • Heiner Boeing
  • Antonia Trichopoulou
  • Pagona Lagiou
  • Dimitrios Trichopoulos
  • Sabina Sieri
  • Domenico Palli
  • Salvatore Panico
  • Petra H. Peeters
  • Elisabete Weiderpass
  • Guri Skeie
  • Paula Jakszyn
  • María Dolores Chirlaque
  • Eva Ardanaz
  • María José Sánchez
  • Roy Ehrnström
  • Börje Ljungberg
  • Kay Tee Khaw
  • Nick J. Wareham
  • Paul Brennan
  • Mattias Johansson
  • Elio Riboli
  • Lambertus A. Kiemeney
Enheter & grupper
Externa organisationer
  • National Institute for Public Health and the Environment (RIVM)
  • Imperial College London
  • University Medical Center Utrecht
  • University of Malaya
  • Wageningen University
  • Danish Cancer Society Research Center
  • INSERM U1018
  • University of Paris-Sud
  • German Cancer Research Centre
  • University Medical Center Hamburg-Eppendorf
  • German Institute of Human Nutrition
  • Vivantes Humboldt Hospital
  • National and Kapodistrian University of Athens
  • Hellenic Health Foundation, Athens
  • Harvard University
  • Academy of Athens
  • Istituto Nazionale dei Tumori
  • University of Naples Federico II
  • UiT The Arctic University of Norway, Tromsø
  • Cancer Registry of Norway Institute of Population-Based Cancer Research
  • Karolinska Institute
  • University of Helsinki
  • Catalan Institute of Oncology
  • University of Murcia
  • Health Research Institute of Navarra (IDISNA)
  • University of Granada
  • Skåne University Hospital
  • Umeå University
  • University of Cambridge
  • International Agency for Research on Cancer, World Health Organization
  • Netherlands Comprehensive Cancer Organisation (IKNL)
  • Institut Gustave Roussy
  • Cancer Research and Prevention Institute
  • Folkhälsans forskningscentrum
  • CIBER Epidemiology and Public Health (CIBERESP)
  • Radboud University Medical Center
  • Radboud University Nijmegen

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
  • Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi


Sidor (från-till)2349-2359
TidskriftInternational Journal of Cancer
Utgåva nummer9
Tidigt onlinedatum2019 jan 29
StatusPublished - 2019
Peer review utfördJa