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Carcinogenesis Advance Access originally published online on October 27, 2006
Carcinogenesis 2007 28(4):848-857; doi:10.1093/carcin/bgl204
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Glutathione S-transferase phenotypes in relation to genetic variation and fruit and vegetable consumption in an endoscopy-based population

Mariken J. Tijhuis1, Marleen H.P.W. Visker1, Jac M.M.J.G. Aarts2, Wilbert H.M. Peters3, Hennie M.J. Roelofs3, Liesbeth Op den Camp2, Ivonne M.C.M. Rietjens2, Anne-Marie J.F. Boerboom2, Fokko M. Nagengast3, Frans J. Kok1 and Ellen Kampman1,*

1 Division of Human Nutrition, Wageningen University Wageningen, The Netherlands
2 Division of Toxicology, Wageningen University Wageningen, The Netherlands
3 Department of Gastroenterology, Radboud University Nijmegen Medical Centre Nijmegen, The Netherlands

*To whom correspondence should be addressed at: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV Wageningen, The Netherlands. Tel: +31 317 48 38 67; Fax: +31 317 48 27 82; E-mail: Ellen.Kampman{at}wur.nl.

High glutathione S-transferase (GST) activity may contribute to colorectal cancer prevention. Functional polymorphisms are known in the GSTM1, GSTT1, GSTA1 and GSTP1 genes. The influence of these GST polymorphisms and recent fruit and vegetable consumption on GST levels and activity has not been investigated simultaneously in a human population. Also, it is not clear if blood GST activity reflects rectal GST activity. Therefore, we determined GST polymorphisms in 94 patients scheduled for sigmoidoscopy. Rectal GST isoenzyme levels (GSTM1, GSTM2, GSTT1, GSTA and GSTP1) were measured by quantitative western blotting, and rectal and white blood cell total GST activities were measured spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. Vegetable and fruit consumption was assessed by dietary record. As expected, the GSTM1 and GSTT1 deletion polymorphisms, and the GSTA1 g.-69C->T polymorphism significantly affected the respective isoenzyme levels. Also, rectal GST isoenzyme levels differed between those with and without recent consumption of Alliaceae, Cucurbitaceae, Apiaceae and citrus fruit. Rectal GST activity, however, was not clearly influenced by fruit and vegetable consumption. It was most significantly determined by the GSTP1 c.313A->G polymorphism; compared with the 313AA genotypes, the 313AG and 313GG genotypes showed 36 and 67 nmol/min/mg protein (P < 0.001) lower GST activity, respectively. The correlation between rectal and white blood cell GST activities was low (r = 0.40, P < 0.001), and the relevance of the various genetic and dietary factors appeared to differ between the two tissues. In conclusion, this study indicates that the GST enzyme system is influenced by both GST polymorphisms and consumption of fruits and vegetables. The latter appeared more important for individual rectal GST isoenzyme levels than for total GST activity, which could affect detoxification of isoenzyme-specific substrates. The study results do no support the use of white blood cell GST activity as a surrogate measure for rectal GST activity.

Abbreviations: CRC, colorectal cancer; GST, glutathione S-transferase; DNP-SG, 2,4-dinitrophenyl-S-glutathione.

Received May 2, 2006; revised September 23, 2006; accepted October 16, 2006.


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