Investigating the role of DNA hypermethylation as a key controller of aberrant cell death in prostate cancer

Abstract

Prostate cancer remains a global public health problem. Worldwide, it is the most common noncutaneous cancer in men and is a leading cause of cancer- related deaths among men in North America and Westem\Northem Europe. Currently, PSA is the screening tool of choice and has been estimated to reduce the rate of death from prostate cancer by 20% but fails to adequately distinguish between clinically indolent versus aggressive forms of prostate cancers. Development, therefore, of novel diagnostic and prognostic markers is imperative to enhance the predictive value of current screening tools. Uncharacteristic DNA methylation has been implicated as a key survival mechanism in cancer, whereby promoter hypermethylation silences genes essential for many important cellular processes, such as apoptosis. Disruption of apoptosis, via both genetic and epigenetic mechanisms is one of the principal factors contributing to the evolution of the carcinogenic phenotype. To date, studies on the methylation profile of apoptotic genes have largely focused on cancers of the breast, colon and stomach, with only limited data available on prostate cancer.