New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid.

TitleNew marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid.
Publication TypeJournal Article
Year of Publication2006
AuthorsPierre, F, Peiro, G, Taché, S, Cross, AJ, Bingham, SA, Gasc, N, Gottardi, G, Corpet, DE, Guéraud, F
JournalCancer Epidemiol Biomarkers Prev
Volume15
Issue11
Pagination2274-9
Date Published2006 Nov
ISSN1055-9965
KeywordsAcetylcysteine, Adult, Aged, Animal Feed, Animals, Biomarkers, Tumor, Colonic Neoplasms, Diet, Female, Heme, Humans, Iron, Male, Middle Aged, Oxidative Stress, Rats, Rats, Inbred F344, Risk
Abstract

BACKGROUND: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F(2)alpha (8-iso-PGF(2)alpha), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake.METHODS: We measured urinary excretion of 8-iso-PGF(2)alpha and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron).RESULTS: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF(2)alpha increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans.CONCLUSION: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk.

DOI10.1158/1055-9965.EPI-06-0085
Alternate JournalCancer Epidemiol. Biomarkers Prev.
Citation Key10.1158/1055-9965.EPI-06-0085
PubMed ID17119057