Genomic damage and malignancy in end-stage renal failure: do advanced glycation end products contribute?

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 mutations 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 genomic damage in ESRD patients has been validated by various biomarkers of DNA lesions. We reviewed the mechanisms 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.