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

• Published in: International journal of cancer Vol. 145; no. 9; pp. 2349 - 2359
• Main Authors: Vrieling, Alina, Bueno‐De‐Mesquita, H. Bas, Ros, Martine M., Kampman, Ellen, Aben, Katja K., Büchner, Frederike L., Jansen, Eugène H., Roswall, Nina, Tjønneland, Anne, Boutron‐Ruault, Marie‐Christine, Cadeau, Claire, Chang‐Claude, Jenny, Kaaks, Rudolf, Weikert, Steffen, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Sieri, Sabina, Palli, Domenico, Panico, Salvatore, Peeters, Petra H., Weiderpass, Elisabete, Skeie, Guri, Jakszyn, Paula, Chirlaque, María‐Dolores, Ardanaz, Eva, Sánchez, María‐José, Ehrnström, Roy, Malm, Johan, Ljungberg, Börje, Khaw, Kay‐Tee, Wareham, Nick J., Brennan, Paul, Johansson, Mattias, Riboli, Elio, Kiemeney, Lambertus A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-11-2019; Wiley; John Wiley and Sons Inc
• Subjects: Aged; B-vitamins; Bioindicators; biomarker; Biomarkers; Biomarkers, Tumor - blood; Bladder cancer; Cancer; Cancer and Oncology; Cancer Epidemiology; Cancer och onkologi; Carcinoma, Transitional Cell - blood; Carcinoma, Transitional Cell - epidemiology; Case-Control Studies; Clinical Medicine; Female; folate; Folic acid; Folic Acid - administration & dosage; Folic Acid - blood; Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi; Health risk assessment; Health risks; Health Sciences; Heterogeneity; Homocysteine; Homocysteine - blood; Humans; Hälsovetenskap; Klinisk medicin; Male; Medical and Health Sciences; Medical disciplines: 700; Medical research; Medicin och hälsovetenskap; Medisinske Fag: 700; Metabolism; Middle Aged; nested case-control; Nutrient status; Odds Ratio; Prospective Studies; Public Health, Global Health, Social Medicine and Epidemiology; Risk Assessment; Smoking; Smoking - blood; Smoking - epidemiology; Urinary Bladder Neoplasms - blood; Urinary Bladder Neoplasms - epidemiology; Urothelial carcinoma; urothelial cell carcinomas; VDP; Vitamin B; Vitamin B 12 - blood; Vitamin B 6 - blood; Vitamin B12; Vitamin B6; Vitamins; urothelial cell carcinomas; folate; biomarker; nested case-control; B-vitamins
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.32165

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.
What's new?
Results of studies on dietary folate and bladder cancer risk are inconsistent. This nested case‐control analysis within the European Prospective Investigation into Cancer and Nutrition is one of the first prospective study investigating associations between pre‐diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). This study suggests that lower serum folate concentrations are associated with increased risk of UCC, in particular aggressive UCC.