Identification of Prostate Cancer Predisposition Genes on the Y Chromosome
Abstract
Scientific objective and rationale: The Y chromosome is passed from a father to his son and defines male sex. It has been suggested that genes present on the Y chromosome may also be involved in increasing risk for prostate cancer. We have performed a unique analysis of independent Y chromosomes in a Utah resource that combines genealogy back to the mid-1800s with cancer data from 1966. This analysis shows that there are certain Y chromosomes associated with elevated prostate cancer risk. Investigation of the Y chromosome is challenging because of how it is inherited (it passes relatively unchanged from a man to all of his sons and can thus be shared by large numbers of related men). Genetic analysis is technically difficult on the Y chromosome, and it has rarely been done for prostate cancer. We believe that there are some genes on the Y chromosome that are related to increased risk and that these specific Y chromosomes can be identified in the Utah genealogy resource. Genetic study of a large number of independent Y chromosomes in Utah, some high risk and some not, will allow us to locate the gene(s) that increase risk for prostate cancer on the Y chromosome. We have been studying high-risk prostate cancer families for over 25 years. We have sampled over 10,000 individuals in over 550 high-risk prostate cancer families. We will identify and study specific Y chromosomes that have more prostate cancer among family members than would be expected by chance. In the Utah Population Data Base, we have identified over 259,000 independent groups of men, each group of men sharing the same Y chromosome from a shared male ancestor (based on genealogy data); we call these YID groups. There are over 5,000 YID groups that have at least 2 cases of prostate cancer; 1,000 of these have more prostate cancer cases than expected. From our family study resource of 30,000 stored blood/DNA samples representing many different diseases in big Utah families, we will analyze already-gathered DNA samples representing independent Y chromosomes. We will look for genetic differences in the Y chromosomes that are associated with more prostate cancer than expected by chance compared to the Y chromosomes that do not. We will efficiently use already sampled males in the Utah genealogy who represent over 800 Y chromosomes. This genetic analysis will tell us a small region(s) on the Y chromosome where we can look to find the gene(s). Ultimate applicability of the research (What types of patients will it help and how? What are the potential clinical applications, benefits, and risks? What is the projected time to achieve a patient-related outcome?): This research will be valuable for all prostate cancer patients. Finding a predisposition gene will allow individualized risk assessment for many families. It will also provide new information about genetic causes of prostate cancer that could lead to new therapies and other new genes identified. These types of outcomes are reasonable in a 5- to 10-year time period. Interim outcomes before clinical applicability: Before clinical applicability, as described above, we are likely to learn more about the genetics of prostate cancer and we are likely to identify additional predisposition genes. Likely contributions of this study to advancing the field of research: Identification of a prostate cancer predisposition gene will have huge significance as so few have been identified. Because most prostate tumors have lost the Y chromosome, genes found there may be especially important. Eventually we can use tests of a man s Y chromosome to find his risk and perhaps develop more precise treatments for prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510638
Entities
People
- Lisa Albright
Organizations
- United States Army
- University of Utah