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

TY - JOUR

T1 - One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

AU - Vrieling, Alina

AU - Bueno-De-Mesquita, H Bas

AU - Ros, Martine M

AU - Kampman, Ellen

AU - Aben, Katja K

AU - Büchner, Frederike L

AU - Jansen, Eugène H

AU - Roswall, Nina

AU - Tjønneland, Anne

AU - Boutron-Ruault, Marie-Christine

AU - Cadeau, Claire

AU - Chang-Claude, Jenny

AU - Kaaks, Rudolf

AU - Weikert, Steffen

AU - Boeing, Heiner

AU - Trichopoulou, Antonia

AU - Lagiou, Pagona

AU - Trichopoulos, Dimitrios

AU - Sieri, Sabina

AU - Palli, Domenico

AU - Panico, Salvatore

AU - Peeters, Petra H

AU - Weiderpass, Elisabete

AU - Skeie, Guri

AU - Jakszyn, Paula

AU - Chirlaque, María-Dolores

AU - Ardanaz, Eva

AU - Sánchez, María-José

AU - Ehrnström, Roy

AU - Malm, Johan

AU - Ljungberg, Börje

AU - Khaw, Kay-Tee

AU - Wareham, Nick J

AU - Brennan, Paul

AU - Johansson, Mattias

AU - Riboli, Elio

AU - Kiemeney, Lambertus A

N1 - © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - Aged

KW - Biomarkers, Tumor/blood

KW - Carcinoma, Transitional Cell/blood

KW - Case-Control Studies

KW - Female

KW - Folic Acid/administration & dosage

KW - Homocysteine/blood

KW - Humans

KW - Male

KW - Middle Aged

KW - Odds Ratio

KW - Prospective Studies

KW - Risk Assessment

KW - Smoking/blood

KW - Urinary Bladder Neoplasms/blood

KW - Vitamin B 12/blood

KW - Vitamin B 6/blood

U2 - 10.1002/ijc.32165

DO - 10.1002/ijc.32165

M3 - SCORING: Journal article

C2 - 30694528

VL - 145

SP - 2349

EP - 2359

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 9

ER -