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Cruciferous Vegetable Feeding Alters UGT1A1 Activity: Diet- and Genotype-Dependent Changes in Serum Bilirubin in a Controlled Feeding Trial

Authors' Affiliations: ¹ Bastyr University, Kenmore, Washington; ² Fred Hutchinson Cancer Research Center, Seattle, Washington; and ³ Department of Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota

Requests for reprints: Johanna W. Lampe, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109. Phone: 206-667-6580; Fax: 206-667-7850; E-mail: jlampe{at}fhcrc.org.

Chemoprevention by isothiocyanates from cruciferous vegetables occurs partly through up-regulation of phase II conjugating enzymes, such as UDP-glucuronosyltransferases (UGT). UGT1A1 glucuronidates bilirubin, estrogens, and several dietary carcinogens. The UGT1A1*28 polymorphism reduces transcription compared with 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, crossover feeding trial in humans (n = 70), three test diets (single- and double-"dose" cruciferous and cruciferous plus apiaceous) compared with 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 with 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 with basal (P < 0.03 for both); *1/*28 in double-dose cruciferous and cruciferous plus apiaceous compared with basal, and cruciferous plus apiaceous compared with single-dose cruciferous (P < 0.02 for all); and *28/*28 in all vegetable-containing diets compared with 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.

Key Words: Isothiocyanates • cruciferous vegetables • UDP-glucuronosyltransferase (UGT) 1A1 • bilirubin • glutathione S-transferase (GST) • apiaceous vegetables • sulforaphane

Commentary

Cruciferous Vegetable Intake and Cancer Prevention: Role of Nutrigenetics

Christine B. Ambrosone and Li Tang
Cancer Prevention Research 2009 2: 298-300. [Full Text] [PDF]

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				F. Li, M. A. J. Hullar, Y. Schwarz, and J. W. Lampe Human Gut Bacterial Communities Are Altered by Addition of Cruciferous Vegetables to a Controlled Fruit- and Vegetable-Free Diet J. Nutr., September 1, 2009; 139(9): 1685 - 1691. [Abstract] [Full Text] [PDF]

				C. B. Ambrosone and L. Tang Cruciferous Vegetable Intake and Cancer Prevention: Role of Nutrigenetics Cancer Prevention Research, April 1, 2009; 2(4): 298 - 300. [Full Text] [PDF]