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

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 and Boutron-Ruault, Marie Christine, et al. (2019) In International Journal of Cancer
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... (More)

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.

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keywords
B-vitamins, biomarker, folate, nested case–control, urothelial cell carcinomas
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International Journal of Cancer
publisher
John Wiley & Sons
external identifiers
  • scopus:85061451074
ISSN
0020-7136
DOI
10.1002/ijc.32165
language
English
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yes
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2968d6c3-1ca6-461f-b15c-c49940cff0b6
date added to LUP
2019-02-22 12:30:48
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2019-03-19 04:06:01
@article{2968d6c3-1ca6-461f-b15c-c49940cff0b6,
  abstract     = {<p>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.</p>},
  author       = {Vrieling, Alina and Bueno-De-Mesquita, H. Bas and Ros, Martine M. and Kampman, Ellen and Aben, Katja K. and Büchner, Frederike L. and Jansen, Eugène H. and Roswall, Nina and Tjønneland, Anne and Boutron-Ruault, Marie Christine and Cadeau, Claire and Chang-Claude, Jenny and Kaaks, Rudolf and Weikert, Steffen and Boeing, Heiner and Trichopoulou, Antonia and Lagiou, Pagona and Trichopoulos, Dimitrios and Sieri, Sabina and Palli, Domenico and Panico, Salvatore and Peeters, Petra H. and Weiderpass, Elisabete and Skeie, Guri and Jakszyn, Paula and Chirlaque, María Dolores and Ardanaz, Eva and Sánchez, María José and Ehrnström, Roy and Malm, Johan and Ljungberg, Börje and Khaw, Kay Tee and Wareham, Nick J. and Brennan, Paul and Johansson, Mattias and Riboli, Elio and Kiemeney, Lambertus A.},
  issn         = {0020-7136},
  keyword      = {B-vitamins,biomarker,folate,nested case–control,urothelial cell carcinomas},
  language     = {eng},
  month        = {01},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition},
  url          = {http://dx.doi.org/10.1002/ijc.32165},
  year         = {2019},
}