Cancer pharmacogenomics: role of DNA repair genetic polymorphisms in individualizing cancer therapy.

The evolving field of cancer pharmacogenomics uses genetic profiling to predict the response of tumor and normal tissue to therapy. The narrow therapeutic index and heterogeneity of patient responses to chemotherapy and radiotherapy implies that the efficacy of these treatments could, potentially, be significantly enhanced by improving our understanding of the genetic bases for interindividual differences in their effects. The cytotoxicity of both chemotherapy and radiotherapy is to a large extent directly related to their ability to induce DNA damage. The ability of cancer cells to recognize and repair this damage contributes to therapeutic resistance. On the other hand, suboptimal DNA repair in normal tissue may negatively impact on normal tissue tolerance. More than 130 genes have been identified that are associated with human DNA repair, and single nucleotide polymorphisms of several of the DNA repair genes have been described recently. In this article, we present the current evidence implicating variations within DNA repair genes as important predictive and prognostic markers in cancer. We review evidence suggesting DNA repair genetic polymorphisms may significantly influence the clinical response to chemotherapy and radiotherapy, and may influence normal tissue tolerance to cancer treatments.