REVIEW Antioxidative and antigenotoxic properties of vegetables and dietary phytochemicals: The value of genomics biomarkers in molecular epidemiology Theo M. C. M. de Kok 1 , Pim de Waard 2 , Lonneke C. Wilms 1 and Simone G. J. van Breda 1 1 Department of Health Risk Analysis and Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands 2 National Institute for Public Health and the Environment, Bilthoven, The Netherlands Received: June 18, 2009 Revised: September 8, 2009 Accepted: September 11, 2009 There is considerable evidence that consumption of fruits and vegetables may contribute to the prevention of cancer. It is however remarkable that evidence for such a preventive action arising from mechanistic studies is becoming stronger, whereas results of some recent prospective studies are less convincing. This apparent discrepancy may be overcome, or at least understood, by introducing molecular markers in future epidemiological studies, taking modulation of molecular processes as well as genetic variability in human populations into account. Both human and animal studies demonstrated that vegetable intake modulates gene expression in the gastrointestinal tract of many genes involved in biological pathways in favor of cancer risk prevention. Gene sets identified in this type of studies can be further evaluated, linked to the biological effects of phytochemicals and developed into biomarkers for larger human studies. Human dietary intervention studies have demonstrated that, apart from target tissues, also peripheral lymphocytes can be used for biomonitoring of chemopreventive effects. Transcriptomic responses and metabolite profiling may link phenotypic markers of preventive effects to specific molecular processes. The use of genomics techniques appears to be a promising approach to establish mechanistic pathways involved in chemoprevention by phytochemicals, particularly when genetic variability is taken into account. Keywords: Antioxidants / Chemoprevention / Genomics biomarkers / Phytochemicals / Vegetables 1 Introduction Epidemiological studies indicate an interactive association between dietary habits, lifestyle, genetics and the risk of many different chronic diseases, including cancer. The most consistent finding on diet as a determinant of cancer risk prevention is the association between consumption of vegetables and fruits and reduced risk of several types of cancers. In order to establish the strength of the evidence for a cancer preventive effect of fruits and vegetables, the World Cancer Research Fund (WCRF) first reviewed the literature in 1997. At that time, the WCRF panel concluded that the evidence for a protective effect for cancers of the colon/ rectum, lung, stomach, esophagus and mouth/pharynx was ‘‘convincing’’, whereas the evidence for such an effect in the larynx, pancreas, breast and bladder was considered ‘‘prob- able’’ [1]. More recently, a number of prospective studies failed to support such protective effects, and as a conse- quence, these initial judgments were adjusted accordingly, both in the IARC handbook of Cancer prevention on Fruits and Vegetables [2] and in the update of the initial WCRF Abbreviations: AhR, aryl hydrocarbon receptor; BPDE, benzo[a]- pyrenediol-epoxide; COMT1, catechol O-methyltransferase 1; CYP, cytochrome P450; GSTT1, glutathione S-transferase T1; NAhRA, natural aryl hydrocarbon receptor agonist; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TEAC, Trolox equivalent antioxidant capacity Correspondence: Dr. Theo M. C. M. de Kok, Department of Health Risk Analysis and Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P. O. Box 616, 6200 MD Maastricht, The Netherlands E-mail: t.dekok@grat.unimaas.nl Fax: 131433884146 & 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com 208 Mol. Nutr. Food Res. 2010, 54, 208–217 DOI 10.1002/mnfr.200900288