Elucidating the Metabolomic Profile of Fatal Prostate Cancer
Abstract
Prostate cancer is the most common cancer diagnosed in men in the United States, and the third leading cause of cancer death. However, scientists’ understanding of what causes prostate cancer is incomplete. The well-established causes are older age, Black race, and having a family history of prostate cancer. Because these things cannot be changed, researchers and doctors are limited in what advice they can give to men about what they can do to prevent prostate cancer. It is well-accepted that many prostate cancer cases that are diagnosed through prostate-specific antigen (PSA) screening are unlikely to progress to death. The causes of these indolent cancers are likely very different from the causes of more aggressive and lethal prostate cancers, so it is very important to study aggressive and fatal prostate cancers separately. However, relatively little work has been done to study these, particularly fatal prostate cancer. Metabolomic profiling is a new laboratory technique that allows researchers to measure hundreds of things at a time in blood or tissue samples. This type of approach is called an agnostic approach, and it can be contrasted with hypothesis-driven approaches. Usually, research is conducted in a hypothesis-driven way: scientists know something about a particular biomarker and suspect, based on what they know about it, that it may cause cancer. They therefore measure that one biomarker and examine it in relation to risk of cancer. In an agnostic approach, we acknowledge that there may be things that cause cancer that we don’t know about or haven’t thought of yet. So instead of choosing what to measure, we measure everything we can and use statistics to see which things are most associated with risk of prostate cancer. Another agnostic approach that has been used for decades is the genome-wide association study, and these studies have been very successful in identifying new genes that are associated with risk of cancer. Thus, we think that metabolomic profiling has similar promise. The metabolomic platform that we plan to use has, in previous studies, measured more than 800 individual metabolites in eight different chemical classes: amino acids and amino acid derivatives, carbohydrates, cofactors and vitamins, energy metabolites, lipids, nucleotides, peptides, and xenobiotics (i.e., chemicals that originate from outside the body, such as caffeine or drug metabolites). We plan to measure the metabolomic profiles of over 2,000 men diagnosed with prostate cancer, using blood that was collected before they had cancer. This way we hope to discover things that might have caused their cancer. We plan to look for metabolites associated with higher-stage or -grade cancers, because these tend to be more aggressive and lead to death, as well as with fatal disease. We then plan to see whether those metabolites are still associated with fatal prostate cancer when we look at men with and without known risk factors for fatal prostate cancer such as smoking, obesity, and having certain genes. This information will be very important because it may identify new things that cause fatal prostate cancer. If these things can be changed, researchers and doctors will be able to tell men what they can do to prevent themselves from developing fatal prostate cancer. If we find things that cannot be changed, we could still identify men at higher risk of fatal prostate cancer and recommend additional screening for those men. Finally, using metabolomics, plus the information we already know about what may cause more aggressive or fatal prostate cancer (smoking, being obese, or having certain genes), might help us determine which men diagnosed with prostate cancer are most likely to die of their disease, allowing doctors to make better treatment recommendations. This work will help move us toward our ultimate goal of eliminating death due to prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810275
Entities
People
- Alison Mondul
Organizations
- United States Army
- University of Michigan