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

Published version
Peer-reviewed

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Authors

Bueno-De-Mesquita, H Bas 
Ros, Martine M 
Kampman, Ellen 
Aben, Katja K 

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.

Description

Keywords

B-vitamins, biomarker, folate, nested case-control, urothelial cell carcinomas, Aged, Biomarkers, Tumor, Carcinoma, Transitional Cell, Case-Control Studies, Female, Folic Acid, Homocysteine, Humans, Male, Middle Aged, Odds Ratio, Prospective Studies, Risk Assessment, Smoking, Urinary Bladder Neoplasms, Vitamin B 12, Vitamin B 6

Journal Title

Int J Cancer

Conference Name

Journal ISSN

0020-7136
1097-0215

Volume Title

145

Publisher

Wiley
Sponsorship
Medical Research Council (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)
Cancer Research Uk (None)
This work has been supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004; Research Directorate-General 2005; Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund (FIS) of the Spanish Ministry of Health, The participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council (United Kingdom); Hellenic Health Foundation, Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity; Italian Association for Research on Cancer, National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Comprehensive Cancer Organisation The Netherlands (IKNL), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Dutch Cancer Society (KWF), Statistics Netherlands (The Netherlands); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane (Sweden); Helga study - Nordforsk center of excellence programme in food and nutrition (Norway). The study sponsors had no role in the design, collection, analysis or interpretation of the data, nor in writing or submitting the manuscript.