title: A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus.
abstract: Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4 vs. Q1 ] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4 vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8×10(-4)), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.
authors: International Agency for Research on Cancer, Lyon, France.
authors: Anouar
authors: A
authors: Fanidi
authors: Caroline
authors: C
authors: Relton
authors: Per Magne
authors: PM
authors: Ueland
authors: Øivind
authors: Ø
authors: Midttun
authors: Stein Emil
authors: SE
authors: Vollset
authors: Ruth C
authors: RC
authors: Travis
authors: Antonia
authors: A
authors: Trichopoulou
authors: Pagona
authors: P
authors: Lagiou
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: H Bas
authors: HB
authors: Bueno-de-Mesquita
authors: Martine
authors: M
authors: Ros
authors: Heiner
authors: H
authors: Boeing
authors: Rosario
authors: R
authors: Tumino
authors: Salvatore
authors: S
authors: Panico
authors: Domenico
authors: D
authors: Palli
authors: Sabina
authors: S
authors: Sieri
authors: Paolo
authors: P
authors: Vineis
authors: María-José
authors: MJ
authors: Sánchez
authors: José María
authors: JM
authors: Huerta
authors: Aurelio
authors: A
authors: Barricarte Gurrea
authors: Leila
authors: L
authors: Luján-Barroso
authors: J Ramón
authors: JR
authors: Quirós
authors: Anne
authors: A
authors: Tjønneland
authors: Jytte
authors: J
authors: Halkjær
authors: Marie-Christine
authors: MC
authors: Boutron-Ruault
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Claire
authors: C
authors: Cadeau
authors: Elisabete
authors: E
authors: Weiderpass
authors: Mikael
authors: M
authors: Johansson
authors: Elio
authors: E
authors: Riboli
authors: Paul
authors: P
authors: Brennan
authors: Mattias
authors: M
authors: Johansson
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D050260:Carbohydrate Metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000401:mortality; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood* / Q000401:mortality; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: EPIC; head and neck cancer; one-carbon metabolism