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

Title: One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
Authors: Vrieling, A
Bueno-De-Mesquita, HB
Ros, MM
Kampman, E
Aben, KK
Büchner, FL
Jansen, EH
Roswall, N
Tjønneland, A
Boutron-Ruault, M-C
Cadeau, C
Chang-Claude, J
Kaaks, R
Weikert, S
Boeing, H
Trichopoulou, A
Lagiou, P
Trichopoulos, D
Sieri, S
Palli, D
Panico, S
Peeters, PH
Weiderpass, E
Skeie, G
Jakszyn, P
Chirlaque, M-D
Ardanaz, E
Sánchez, M-J
Ehrnström, R
Malm, J
Ljungberg, B
Khaw, K-T
Wareham, NJ
Brennan, P
Johansson, M
Riboli, E
Kiemeney, LA
Item Type: Journal Article
Abstract: 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.
Issue Date: 1-Nov-2019
Date of Acceptance: 4-Jan-2019
ISSN: 0020-7136
Publisher: Wiley
Start Page: 2349
End Page: 2359
Journal / Book Title: International Journal of Cancer
Volume: 145
Issue: 9
Copyright Statement: © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: SP23-CT-2005-006438
Keywords: Science & Technology
Life Sciences & Biomedicine
urothelial cell carcinomas
nested case-control
nested case-control
urothelial cell carcinomas
nested case-control
urothelial cell carcinomas
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-01-29
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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