title: A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.
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.
authors.affiliation: School of Public Health, Imperial College London, London, UK.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Chuang
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Sophie
authors.initials: S
authors.lastname: Morois
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Birgit
authors.initials: B
authors.lastname: Teucher
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
authors.forename: Heiner
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authors.lastname: Boeing
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Benetou
authors.forename: Androniki
authors.initials: A
authors.lastname: Naska
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Michaud
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Guri
authors.initials: G
authors.lastname: Skeie
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodriguez
authors.forename: Esther
authors.initials: E
authors.lastname: Molina-Montes
authors.forename: José Marı A
authors.initials: JM
authors.lastname: Huerta
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Aurelio Barricarte
authors.initials: AB
authors.lastname: Gurrea
authors.forename: Dorthe
authors.initials: D
authors.lastname: Johansen
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jeurnink
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wareham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Francesca
authors.initials: F
authors.lastname: Crowe
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Bas
authors.initials: B
authors.lastname: Bueno-de-Mesquita
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D015992:Body Mass Index; D016022:Case-Control Studies; D003367:Cotinine / Q000097:blood; D004268:DNA-Binding Proteins / Q000097:blood; D048909:Diabetes Complications / Q000139:chemically induced / Q000517:prevention & control; D005060:Europe / Q000453:epidemiology; D005260:Female; D005486:Flavin Mononucleotide / Q000097:blood; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D011446:Prospective Studies; D011732:Pyridoxal Phosphate / Q000097:blood; D012256:Riboflavin / Q000097:blood; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D014157:Transcription Factors / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood; D014803:Vitamin B Complex / Q000097:blood
chemical_list: D004268:DNA-Binding Proteins; C078341:MYT1 protein, human; D014157:Transcription Factors; D006710:Homocysteine; D014803:Vitamin B Complex; D011732:Pyridoxal Phosphate; D005486:Flavin Mononucleotide; D005492:Folic Acid; D008715:Methionine; D003367:Cotinine; D014805:Vitamin B 12; D012256:Riboflavin