Prospective Personal Biomarkers of Late-Stage and Lethal Prostate Cancer in African Americans
Abstract
Rationale: Many prostate cancers never become aggressive and life-threatening, and most men have the beginnings of prostate cancers that you can see in men who die of another cause. However, for African Americans, prostate cancer is more likely to start aggressively at a younger age and to be lethal. Because screening for prostate cancer and unnecessary treatment can cause serious complications like impotence, it is now recognized that it is terribly important to find a way to determine which prostate cancers need to be treated right away. This is particularly important for African Americans who are younger when cancer is found and more likely to die of prostate cancer. It is thought that a clue to why some prostate cancers become lethal is related to how the cells that make up the prostate get their energy through cell components called mitochondria. These energy factories are very sensitive to many signals within and outside the body, including diet, stress, hormones, chemicals, and exposures from the environment and workplace. We think that African Americans have more exposures that change the function of mitochondria and promote the growth of prostate cancers, making them become aggressive and lethal. Therefore, we want to find the chemicals in human blood samples taken from young men (in their 30s) that correlate with future lethal prostate cancer, as well as with the environmental factors that could be changed to protect them and future generations. Some of the chemical pathways that are overdeveloped in the body might be controlled now with existing medications (just like we use cholesterol as a marker for heart problems that we control with drugs that lower cholesterol). Knowing the chemical biomarkers that are linked to lethal disease can be used immediately to find men whose cancers need treatment to avoid death. In addition, by looking at environments that promote dangerous chemical pathways in the body, we will create a strategy for advocacy to reduce those factors—whether they are behaviors like smoking or things that we cannot control personally, like air pollution and pesticides in the environment. Objectives: We already know that African Americans have higher exposures to some environmental toxins and to some forms of stress related to lower income and discrimination. We need to know now whether any of the pathways linked to these inside the body are also linked to lethal prostate cancer. Animal studies show that these pathways may do damage before birth, making the prostate even more sensitive to insults after birth. We want to see whether that can be confirmed in humans at high risk: African Americans as well as whites. If so, then protecting young people before they are parents and during pregnancy may be a way to break the generation-to-generation transfer of risk for lethal prostate cancer. The environment may be more important than genes, given that prostate cancer is not usually inherited. There are new research tools that can measure thousands of chemicals that the body makes in response to the environment, as well as the chemicals that a person takes in from the environment (High-Resolution Metabolomics, HRM). We will use these tools in a unique existing 60-year, two-generation study Child Health and Development Studies (CHDS) population that is a representative sample of Alameda County, California, in the 1960s with a sizeable African American population. We want to see which of these chemicals predicts lethal or early prostate cancer. Aims: Our main aim is to test whether the chemicals that are made inside a man’s body and are measured in blood samples donated by young adult men (mean age of 34) predict lethal prostate later in life in African Americans and whites in the CHDS fathers generation. Our riskier new idea: For the first time ever, we will test whether chemicals made in a person’s body and chemicals from the environment (like pesticides and air pollution) that
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110212
Entities
People
- Barbara A Cohn
Organizations
- Public Health Institute
- United States Army