Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Kidney Blood Press Res 2007;30:56–66 DOI: 10.1159/000099029 Genomic Damage and Malignancy in End-Stage Renal Failure: Do Advanced Glycation End Products Contribute? Katarína Šebeková a Zoltán Wagner b Nicole Schupp c Peter Boor a a Department of Experimental and Clinical Pharmacotherapy, Research Base of Slovak Medical University, Bratislava, Slovakia; b Second Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary; c Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany nisms of DNA damage, focusing in particular on the role of advanced glycation end products (AGEs) which accumulate markedly in renal insufficiency. Considering the in vitro and in vivo findings to date, one has to assume a significant role of AGEs in DNA damage and the potential development of cancer. Copyright © 2007 S. Karger AG, Basel Incidence of Cancer in End-Stage Renal Disease In end-stage renal disease (ESRD) patients the relative risk of cancer is enhanced [1]. However, this increase is not uniform: the standardized incidence ratio, i.e. the number of patients who developed cancer compared with an expected number, is much higher for tumors of the kidney, bladder, liver, prostate, thyroid gland, oral cavity and hemopoietic system (table 1 ) [2–6]. A less marked or lack of increase has been observed for malignancies of the stomach, bronchi, lungs, colon, rectum, sigma and breast (table 1) [2–4]. Similar to cardiovascular diseases, the in- cidence of the majority of the cancers is much higher in younger patients and decreases with ageing [2–4] . The majority of tumors is diagnosed particularly within the Key Words Advanced glycation end products, receptor for  End-stage renal disease  Dialysis  Cancer  Reactive oxygen species  Glyoxal  Methylglyoxal  3-Deoxyglucosone  N  -Carboxymethyl(lysine) Abstract In end-stage renal disease (ESRD) there is not only excessive morbidity and mortality due to cardiovascular disease but also an enhanced occurrence of various types of cancer. Both are characterized by oxidative stress and inflammation as two of the central underlying causes of the disease states. In cancer, genomic damage has been demonstrated to be of high pathogenetic relevance. DNA lesions may induce muta- tions of oncogenes and tumor-suppressor genes which, in the long-run, may lead to malignancies if mutagenicity is not mitigated by repair mechanisms. A high incidence of ge- nomic damage in ESRD patients has been validated by vari- ous biomarkers of DNA lesions. We reviewed the mecha- Published online: January 25, 2007 Katarína Šebeková, MD, DSc Research Base of Slovak Medical University Department of Clinical and Experimental Pharmacotherapy, Limbová 14 SK–833 03 Bratislava 37 (Slovakia) Tel. +421 2 59369 431, Fax +421 2 59369 170, E-Mail katarina.sebekova@szu.sk © 2007 S. Karger AG, Basel 1420–4096/07/0301–0056$23.50/0 Accessible online at: www.karger.com/kbr This invited review was supported by an unrestricted educational grant provided by Amgen.