Grant: Team Grant: CEEHRC Phase II

While most newly diagnosed prostate cancers are curable, some men will have their cancer return after treatment, often within 1-2 years. These men need more aggressive treatment to prevent the cancer from spreading and threatening their lives. Unfortunately, doctors cannot accurately distinguish curable from aggressive cancer, and better tools are urgently needed to tailor treatments for individual men. This would result in fewer men being treated for non-life threatening cancers, reducing unnecessary side effects such as sexual dysfunction and incontinence, and would allow more aggressive treatment for men who require it, increasing the number of cancers that are ultimately cured. We propose to lead an international effort to profile a type of chemical modification of DNA, known as methylation, taken from 600 prostate cancers. Methylation is involved in turning genes off, and the pattern of methylation in a given cancer may be an important factor in distinguishing between curable and aggressive disease. Thus, we will identify methylation patterns present in life-threatening prostate cancer but not in curable disease. We will then test whether environmental factors such exposure to pesticides and socio-economic status can cause changes in DNA methylation, giving rise to aggressive prostate cancer, and test if inherited DNA mutations influence methylation and aggression. Finally, we will study the economic impact of using DNA methylation patterns in the prostate cancer clinic to identify life-threatening prostate cancer. At the conclusion of our study, we will have developed a DNA methylation test that accurately identifies men who are at the highest risk of aggressive, life-threatening prostate cancer. We will also determine how our test is affected by a man's exposure to common environmental factors and by the man's family history. Finally, we will have produced the evidence necessary to implement our DNA methylation test in the prostate cancer clinic.