Germline Genetics and Prostate Cancer Evolution and Aggressivity

Posted by Paul Boutros, PhD, MBA | Sep 2022

Paul Boutros, PhD, MBA, presented “Germline Genetics and Prostate Cancer Evolution and Aggressivity” during the virtual 5th Global Summit on Precision Diagnosis and Treatment of Prostate Cancer in September 2021.

How to cite: Boutros, Paul. “Germline Genetics and Prostate Cancer Evolution and Aggressivity.” September 2021. Accessed Apr 2024. https://grandroundsinurology.com/germline-genetics-and-prostate-cancer-evolution-and-aggressivity-2021/

Germline Genetics and Prostate Cancer Evolution and Aggressivity – Summary

Paul C. Boutros, PhD, MBA, Professor of Human Genetics and Urology at the University of California, Los Angeles, examines germline genetics and urine characteristics of prostate cancer and how these relate to disease aggressivity and progression. Dr. Boutros poses a question: How significant is germline in prostate cancer relative to other cancer types? He makes the point that prostate cancer is one of the most heritable cancers, citing a group of genome-wide association studies (GWAS) and emphasizes that results showed that in study of common variants present in at least five percent of the population, genetic components alone identified a 25 fold variation in prostate cancer risk. He then addresses more rare variants, the most common of which is BRCA2, a variant associated with very aggressive disease. Dr. Boutros poses another question: Does germline influence prostate cancer evolution? Dr. Boutros described research conducted by a member of his team, graduate student Katie Houlahan, that examined 400 tumors to attempt to associate germline with the effects that happen in a tumor. The research showed a direct relationship between risk single nucleotide polymorphisms (SNPs) and tumor methylation changes; many of these relationships were tumor-specific and prognostic. Dr. Boutros then discusses germline and somatic mutations in BRCA2, sharing data that shows the BRCA2 carriers had much more DNA damage occurring in their tumors than do those with sporadic cases. Dr. Boutros then turns the discussion to urine and explains first that research has shown that urine profiles are longitudinally stable. He displays data showing that, in the characteristics that are longitudinally stable, urine miRNAome correlates to tissue miRNAome. This can provide a biomarker to help inform prognosis in prostate cancer patients. Dr. Boutros describes research that looked at over 1,600 urine proteomes from about 700 patients and they were able to quantify the contributions of prostate, kidney, and bladder to urine protein. Dr. Boutros summarizes by explaining that the prostate cancer germline is a strong driver of tumor incidence and evolution; he reiterates that urine is remarkably stable over time in a single patient and can be an effective biomarker.

The Virtual Global Summit on Precision Diagnosis and Treatment of Prostate Cancer brings together key international opinion leaders of every clinical subspecialty involved in patient care. This event is an integral part of the AdMeTech Foundation’s Annual Summit, which was established in 2016 and became seminal in shaping the state of the art and future vision for precision care. The goal of this event is three-fold: 1) Educating the key stakeholders; 2) Supporting a sustained cross-disciplinary dialogue and consensus on the best emerging clinical practices and research priorities; and 3) Expediting clinical adoption of promising novel diagnostics and therapeutics. For more educational activities from this virtual event, visit our collection page.

About The Author

Paul Boutros, PhD, MBA

Paul C. Boutros, MD, PhD, is a Professor of Human Genetics and Urology at the University of California, Los Angeles. Through UCLA Health, he also runs the Dr. Paul Boutros Lab on Cancer Data Sciences. He earned a BSc degree in Chemistry from the University of Waterloo in Ontario before pursuing a PhD in Medical Biophysics at the Ontario Cancer Institute of the University of Toronto. He also earned his MBA from the Rothman School of Management of the University of Toronto. After receiving his PhD, Dr. Boutros pursued an independent research career as a Fellow and then as a Principal Investigator at the Ontario Institute for Cancer Research. He also served as an Assistant Professor in the Departments of Pharmacology & Toxicology and Medical Biophysics at the University of Toronto. He relocated to UCLA in 2018. Dr. Boutros’ research focuses on personalizing therapy for cancer by developing novel statistical methodologies. His Cancer Data Sciences Lab uses computational techniques to analyze large data sets to create diagnostics to personalize cancer therapy. He largely focuses on prostate cancer, but his lab is increasingly applying the same computational techniques to other cancers, including kidney and bladder cancers. Dr. Boutros has received numerous awards and accolades. He is the recipient of the Terry Fox New Investigator Award, a University of Waterloo Young Alumni Award, the Early Career Graduate Student Teaching Award, and the Dorval Prize of the Canadian Cancer Society. He has also been recognized as a Prostate Cancer Canada Rising Star in Prostate Cancer Research.

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