Genetic epidemiology of mismatch repair deficiency in ovarian cancer

Abstract

This chapter reviews the molecular and histopathologic characteristics of ovarian cancers due to genetic defects in the MMR pathway, highlighting the clinical significance of these findings, including implications for diagnosis, prognosis and treatment as well as interactions between DNA mismatch repair (MMR) pathway and environmental risk factors for ovarian cancer. At least ten per cent of cases of ovarian cancer are due to mutations in BRCA1 and BRCA2 and an additional percentage are due to mutations in other genes, including the mismatch repair genes, MSH2, MLH1 and MSH6. Since the mismatch repair pathway may be impaired in up to one-fifth of ovarian tumors, categorization of ovarian cancers into subtypes based on mismatch repair deficiency is likely to permit more accurate assessment of potential etiologic associations. Furthermore, specific chemotherapeutic regimens may exist specifically for ovarian cancers with microsatellite instability, to improve treatment efficacy and reduce toxicity of drugs which may provide no added benefit. Hence clarification of epigenetic-environment interactions in a large-scale study of ovarian cancers may stimulate the development of novel chemotherapy agents. © 2010 Springer Science+Business Media, LLC.