@article{3187524,
    title = "One-carbon metabolism biomarkers and risk of urothelial cell carcinoma
in the European prospective investigation into cancer and nutrition",
    author = "Vrieling, Alina and Bueno-De-Mesquita, H. Bas and Ros, Martine M. and and Kampman, Ellen and Aben, Katja K. and Buchner, Frederike L. and Jansen, and Eugene H. and Roswall, Nina and Tjonneland, Anne and Boutron-Ruault, and Marie-Christine and Cadeau, Claire and Chang-Claude, Jenny and Kaaks, and Rudolf and Weikert, Steffen and Boeing, Heiner and Trichopoulou, Antonia and and Lagiou, Pagona and Trichopoulos, Dimitrios and Sieri, Sabina and and Palli, Domenico and Panico, Salvatore and Peeters, Petra H. and and Weiderpass, Elisabete and Skeie, Guri and Jakszyn, Paula and Chirlaque, and Maria-Dolores and Ardanaz, Eva and Sanchez, Maria-Jose and Ehrnstrom, and Roy and Malm, Johan and Ljungberg, Borje and Khaw, Kay-Tee and Wareham, and Nick J. and Brennan, Paul and Johansson, Mattias and Riboli, Elio and and Kiemeney, Lambertus A.",
    journal = "International Journal  of Cancer",
    year = "2019",
    volume = "145",
    number = "9",
    pages = "2349-2359",
    publisher = "Wiley",
    issn = "0020-7136",
    doi = "10.1002/ijc.32165",
    keywords = "urothelial cell carcinomas; folate; B-vitamins; biomarker; nested
case-control",
    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."
}