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Cruciferous vegetable feeding alters UGT1A1 activity: diet- and genotype-dependent changes in serum bilirubin in a controlled feeding trial.

Navarro, Sandi L. and Peterson, Sabrina and Chen, Chu and Makar, Karen W. and Schwarz, Yvonne and King, Irena B. and Li, Shuying S. and Li, Lin and Kestin, Mark and Lampe, Johanna W. (2009) Cruciferous vegetable feeding alters UGT1A1 activity: diet- and genotype-dependent changes in serum bilirubin in a controlled feeding trial. Cancer Prevention Research, 2 (4). pp. 345-356. ISSN 1940-6215

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Abstract

Chemoprevention by isothiocyanates from cruciferous vegetables occurs partly through up-regulation of phase-II conjugating enzymes, such as UDP-glucuronosyl-transferases (UGT). UGT1A1 glucuronidates bilirubin, estrogens, and several dietary carcinogens. The UGT1A1*28 polymorphism reduces transcription compared to the wild-type, resulting in decreased enzyme activity. Isothiocyanates are metabolized by glutathione-S-transferases (GST); variants may alter isothiocyanate clearance, such that response to crucifers may vary by genotype. We evaluated, in a randomized, controlled, cross-over feeding trial in humans (n=70), 3 test diets, (single- and double-“dose” cruciferous and cruciferous plus apiaceous) compared to a fruit-and-vegetable-free basal diet. We measured serum bilirubin concentrations on days 0, 7, 11 and 14 of each 2-week feeding period to monitor UGT1A1 activity, and determined effects of UGT1A1*28 and GSTM1/GSTT1-null variants on response. Aggregate bilirubin response to all vegetable-containing diets was statistically significantly lower compared to the basal diet (p<0.03 for all). Within each UGT1A1 genotype, lower bilirubin concentrations were seen in: *1/*1 in both single and double-dose cruciferous diets compared to basal (p<0.03 for both); *1/*28 in double-dose cruciferous and cruciferous plus apiaceous compared to basal, and cruciferous plus apiaceous compared to single-dose cruciferous (p<0.02 for all); and *28/*28 in all vegetable-containing diets compared to basal (p<0.02 for all). Evaluation of the effects of diet stratified by GST genotype revealed some statistically significant genotypic differences however, the magnitude was similar and not statistically significant between genotypes. These results may have implications for altering carcinogen metabolism through dietary intervention, particularly among UGT1A1*28/*28 individuals.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above for the first 12 months post-publication.
DOI: 10.1158/1940-6207.CAPR-08-0178
PubMed ID: 19336732
NIHMSID: NIHMSID91408
PMCID: PMC2666928
Grant Numbers: R01CA070913-08, R01CA092288-04
Keywords or MeSH Headings: * Adult * Bilirubin/blood * Cross-Over Studies * Diet* * Female * Genotype * Glucuronosyltransferase/genetics* * Glucuronosyltransferase/metabolism* * Glutathione Transferase/genetics * Humans * Male * Polymerase Chain Reaction * Polymorphism, Single Nucleotide * Vegetables/metabolism*
Subjects: Health Care > Risk and Preventive Health Services > Diet
Research Methodologies > Epidemiology
Depositing User: Library Staff
Date Deposited: 29 Jan 2009 00:16
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/244

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