Genomic Determinants of Aggressive Prostate Cancer in Obese Men
Abstract
Like all cancers, prostate cancer is caused by changes (“mutations”) in the genetic material (DNA) of normal cells. As these mutations accumulate, the cells begin to grow and to make new copies of themselves more quickly than normal, eventually resulting in a tumor. Over a quarter of a million men are diagnosed with prostate cancer every year in North America. However, most are diagnosed before the cancer has spread outside of the prostate gland, and these men can often be cured with either radiation or surgery. For some men, however, the cancer will return, sometimes within 1-2 years, and these men need more aggressive treatment to prevent the cancer from spreading and threatening their lives. Many of these treatments are lifelong and have significant side effects that can severely affect a man’s quality of life. Unfortunately, the tools that are currently available to doctors do not accurately tell which cancers are curable with standard treatments and which require more aggressive treatment for cure. Better tools are urgently needed to allow doctors to recommend treatments that are appropriate for an individual man with prostate cancer. If such a tool were available, it would result in fewer men getting treated aggressively for cancers that will never threaten their life, therefore reducing unnecessary side effects such as sexual dysfunction and incontinence. It would also allow earlier, more aggressive treatment for men who truly require it, increasing the number of men who are cured of their prostate cancer. Obese men are at very high risk for aggressive, life-threatening prostate cancer. Unfortunately, very little is known about how prostate cancer develops over time in obese men and why the disease is more aggressive for these men. It is also not known whether doctors can use the same tools to identify aggressive disease in obese men as they do in non-obese men. Because the rates of both obesity and prostate cancer are increasing in North America, it is vital to better understand why prostate cancer is often so aggressive in obese men and to develop tools that accurately identify this aggressive disease. This knowledge would allow doctors to treat these men earlier and more effectively and therefore to increase the number of men who are cured of their aggressive, potentially life-threatening prostate cancer. In the first part of this proposal, we will study the mutations found in the DNA of prostate cancers from over 200 obese men. Using a technique known as whole-genome sequencing, we will read the entire genetic code of these cancers to see how these mutations are different from those found in non-obese men or in obese men with less aggressive prostate cancer. We will also test whether sets of these DNA mutations (“signatures”) could be used by doctors as tests to accurately determine which men have potentially life-threatening disease and should be offered more aggressive treatments to be cured of their prostate cancer. In the second part of the proposal, we will study how these mutations affect the growth and spread of prostate cancer cells grown in a dish. We will also test the effect of these mutations on human tumors grown in obese mice. The spread of cancer cells outside of the prostate gland (“metastasis”) is the cause of lethal prostate cancer; therefore, it is critical to understand why some tumors spread more easily than others and how mutations found in prostate cancers in obese men may affect this spread. As the North American population ages, the number of men diagnosed with prostate cancer will continue to increase, as will the number of men suffering from obesity. The results of this study will significantly improve our understanding of the biological differences between prostate cancer in obese and non-obese men. The study will also determine whether doctors can use sets of DNA mutations to test whether an individual man is at high risk of having life-threatening prostate can
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910801
Entities
People
- Philip Awadalla
Organizations
- Ontario Institute for Cancer Research
- United States Army