Cruciferous vegetable feeding alters UGT1A1 activity: diet- and genotype-dependent changes in serum bilirubin in a controlled feeding trial
Navarro SL, Peterson S, Chen C, Makar KW, Schwarz Y, King IB, Li SS, Li L, Kestin M, Lampe JW
Cancer prevention research (Philadelphia, Pa.) · 45 citas
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
- Consumo medido con
- Comida provista por los investigadores
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
- Gobierno
- National Cancer Institute
- Gobierno
- NCI NIH HHS
- Subvenciones
- National Cancer Institute (R01 CA 92288); National Cancer Institute (R01CA070913); National Cancer Institute (R01 CA092288)
Según 3 financiadores declarados.
Publicación
- Publicado
- 2009-03-31 · Cancer Prev Res (Phila) · vol. 2 · número 4 · págs. 345–352
- Editorial
- American Association for Cancer Research
- Citado
- 55 citas · más que el 88% de estudios similares · 2.3× el promedio de su campo
- Referencias
- 51 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Glutathione Transferases and Polymorphisms · Genomics, phytochemicals, and oxidative stress · Pharmacogenetics and Drug Metabolism
- Palabras clave
- cruciferous vegetables, UGT1A1, UGT1A1*28 polymorphism, serum bilirubin, isothiocyanates, phase II conjugation, UDP-glucuronosyltransferase, glutathione S-transferase, GSTM1, GSTT1, dietary chemoprevention, gene-diet interaction, enzyme induction
- MeSH
- humans, vegetables, bilirubin, glutathione transferase, glucuronosyltransferase, diet, cross-over studies, polymerase chain reaction, genotype, polymorphism, single nucleotide, adult, female, male, ugt1a1 enzyme
10 autores
- Sandi L. Navarro🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Sabrina P. Trudo🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Chu Chen🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Karen W. Makar🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Yvonne Schwarz🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Irena B. King🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Shuying S. Li🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Lin Li🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Mark Kestin🇺🇸University of Minnesota; Bastyr University; Fred Hutch Cancer Center
- Johanna W. Lampe🇺🇸 · autor de correspondenciaUniversity of Minnesota; Bastyr University; Fred Hutch Cancer Center
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
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