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A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus

Lookup NU author(s): Professor Caroline Relton

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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 [ORQ4vs. 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 (ORQ4vs. 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 x 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.What's new? One-carbon metabolism (OCM) involves the transfer of a carbon unit from methyl donor nutrients to molecules involved in the synthesis and methylation of DNA. As a result, dietary imbalances or deficiencies in nutrients crucial for OCM may affect DNA replication, repair, and regulation, potentially facilitating cancer development. This analysis of circulating levels of OCM nutrients in head and neck cancer and esophageal cancer patients and matched controls reveals an association between elevated levels of the amino acid homocysteine and increased risk of squamous cell carcinoma of the head and neck. Risk was decreased slightly by elevated folate levels.

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Author(s): Fanidi A, Relton C, Ueland PM, Midttun O, Vollset SE, Travis RC, Trichopoulou A, Lagiou P, Trichopoulos D, Bueno-de-Mesquita HB, Ros M, Boeing H, Tumino R, Panico S, Palli D, Sieri S, Vineis P, Sanchez MJ, Huerta JM, Gurrea AB, Lujan-Barroso L, Quiros JR, Tjonneland A, Halkjaer J, Boutron-Ruault MC, Clavel-Chapelon F, Cadeau C, Weiderpass E, Johansson M, Riboli E, Brennan P, Johansson M

Publication type: Article

Publication status: Published

Journal: International Journal of Cancer

Year: 2015

Volume: 136

Issue: 4

Pages: 915-927

Print publication date: 15/02/2015

Online publication date: 07/07/2014

Acceptance date: 20/05/2014

ISSN (print): 0020-7136

ISSN (electronic): 1097-0215

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1002/ijc.29051

DOI: 10.1002/ijc.29051

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