Population-Based Identification of Prostate Cancer
Abstract
Prostate cancer (PrCa) is the most common cancer diagnosed in the US and one of the most familial. There is evidence for an inherited contribution to PrCa. Analysis of PrCa pedigrees led to discovery of genes that explain a small number of pedigrees (ELAC2, RNASEL, and HOXB13); and more than 100 common genetic variants have been reported to confer modest risk to PrCa.However, taken together, these recognized genetic risk factors explain few pedigrees. The likely genetic heterogeneity of PrCa and lack of success in gene identification suggests a different approach is needed to identify responsible predisposition genes. Analysis of related cases in extended high-risk cancer pedigrees is a powerful approach for identification of cancer predisposition genes. In Utah a resource in combining the genealogy of the pioneer founders and their descendants with Utah cancer data allows identification of extended high-risk prostate cancer pedigrees. Analysis of the most clinically significant PrCa cases (those who die from their disease- lethal PrCa or LPrCa) in these pedigrees further enhances the power of this approach. Objective/Hypothesis: We previously used the same high-risk pedigree approach proposed here to identify multiple cancer predisposition genes in the Utah population (BRCA1- Miki, 1994; BRCA2- Wooster, 1994; CDKN2A- Kamb, 1994). We propose that whole genome sequencing (WGS) of pairs of related LPrCa cases from high-risk PrCa pedigrees and identification of the rare variants shared in these pairs will similarly lead to identification of rare variants in genes that underlie predisposition to PrCa. Extended high-risk pedigrees are likely to evidence a strong role for genetic factors, and the LPrCa case pairs to be sequenced are selected for clinical significance (death from PrCa) to ensure that they exhibit limited genetic heterogeneity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1152373
Entities
People
- L A Cannon-albright
Organizations
- University of Utah