A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

TitleA U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.
Publication TypeJournal Article
Year of Publication2011
AuthorsChuang S-C, Stolzenberg-Solomon R, Ueland P M, Vollset S E, Midttun Ø, Olsen A, Tjønneland A, Overvad K, Boutron-Ruault M-C, Morois S, Clavel-Chapelon F, Teucher B, Kaaks R, Weikert C, Boeing H, Trichopoulou A, Benetou V, Naska A, Jenab M, Slimani N, Romieu I, Michaud DS, Palli D, Sieri S, Panico S, Sacerdote C, Tumino R, Skeie G, Duell EJ, Rodriguez L, Molina-Montes E, Huerta J MA, Larrañaga N, Gurrea A B, Johansen D, Manjer J, Ye W, Sund M, Peeters PHM, Jeurnink S, Wareham N, Khaw K-T, Crowe F, Riboli E, Bueno-de-Mesquita B, Vineis P
JournalEur J Cancer
Volume47
Issue12
Pagination1808-16
Date Published2011 Aug
ISSN1879-0852
KeywordsAdult, Aged, Alcohol Drinking, Body Mass Index, Case-Control Studies, Cotinine, Diabetes Complications, DNA-Binding Proteins, Europe, Female, Flavin Mononucleotide, Folic Acid, Follow-Up Studies, Homocysteine, Humans, Logistic Models, Male, Methionine, Middle Aged, Odds Ratio, Pancreatic Neoplasms, Prospective Studies, Pyridoxal Phosphate, Riboflavin, Risk Factors, Sex Factors, Smoking, Transcription Factors, Vitamin B 12, Vitamin B Complex
Abstract

Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (± 1 year), date (± 1 year) and time (± 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ≤ 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI=0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.17, 95% CI=1.00-1.38) but not in women (OR=0.91, 95% CI=0.78-1.07; p for heterogeneity <0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

DOI10.1016/j.ejca.2011.02.007
Alternate JournalEur. J. Cancer
PubMed ID21411310