HGG Advances (Jan 2022)
Genetic factors associated with prostate cancer conversion from active surveillance to treatment
- Yu Jiang,
- Travis J. Meyers,
- Adaeze A. Emeka,
- Lauren Folgosa Cooley,
- Phillip R. Cooper,
- Nicola Lancki,
- Irene Helenowski,
- Linda Kachuri,
- Daniel W. Lin,
- Janet L. Stanford,
- Lisa F. Newcomb,
- Suzanne Kolb,
- Antonio Finelli,
- Neil E. Fleshner,
- Maria Komisarenko,
- James A. Eastham,
- Behfar Ehdaie,
- Nicole Benfante,
- Christopher J. Logothetis,
- Justin R. Gregg,
- Cherie A. Perez,
- Sergio Garza,
- Jeri Kim,
- Leonard S. Marks,
- Merdie Delfin,
- Danielle Barsa,
- Danny Vesprini,
- Laurence H. Klotz,
- Andrew Loblaw,
- Alexandre Mamedov,
- S. Larry Goldenberg,
- Celestia S. Higano,
- Maria Spillane,
- Eugenia Wu,
- H. Ballentine Carter,
- Christian P. Pavlovich,
- Mufaddal Mamawala,
- Tricia Landis,
- Peter R. Carroll,
- June M. Chan,
- Matthew R. Cooperberg,
- Janet E. Cowan,
- Todd M. Morgan,
- Javed Siddiqui,
- Rabia Martin,
- Eric A. Klein,
- Karen Brittain,
- Paige Gotwald,
- Daniel A. Barocas,
- Jeremiah R. Dallmer,
- Jennifer B. Gordetsky,
- Pam Steele,
- Shilajit D. Kundu,
- Jazmine Stockdale,
- Monique J. Roobol,
- Lionne D.F. Venderbos,
- Martin G. Sanda,
- Rebecca Arnold,
- Dattatraya Patil,
- Christopher P. Evans,
- Marc A. Dall’Era,
- Anjali Vij,
- Anthony J. Costello,
- Ken Chow,
- Niall M. Corcoran,
- Soroush Rais-Bahrami,
- Courtney Phares,
- Douglas S. Scherr,
- Thomas Flynn,
- R. Jeffrey Karnes,
- Michael Koch,
- Courtney Rose Dhondt,
- Joel B. Nelson,
- Dawn McBride,
- Michael S. Cookson,
- Kelly L. Stratton,
- Stephen Farriester,
- Erin Hemken,
- Walter M. Stadler,
- Tuula Pera,
- Deimante Banionyte,
- Fernando J. Bianco, Jr.,
- Isabel H. Lopez,
- Stacy Loeb,
- Samir S. Taneja,
- Nataliya Byrne,
- Christopher L. Amling,
- Ann Martinez,
- Luc Boileau,
- Franklin D. Gaylis,
- Jacqueline Petkewicz,
- Nicholas Kirwen,
- Brian T. Helfand,
- Jianfeng Xu,
- Denise M. Scholtens,
- William J. Catalona,
- John S. Witte
Affiliations
- Yu Jiang
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA
- Travis J. Meyers
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA
- Adaeze A. Emeka
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Lauren Folgosa Cooley
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Phillip R. Cooper
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Nicola Lancki
- Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Irene Helenowski
- Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Linda Kachuri
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA
- Daniel W. Lin
- Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Public Health Sciences, Seattle, WA 98109, USA; Department of Urology, University of Washington, Seattle, WA 98195, USA
- Janet L. Stanford
- Fred Hutchinson Cancer Research Center, Cancer Epidemiology Program, Public Health Sciences, Seattle, WA 98109, USA; Department of Epidemiology, University of Washington, School of Public Health, Seattle, WA 98195, USA
- Lisa F. Newcomb
- Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Public Health Sciences, Seattle, WA 98109, USA; Department of Urology, University of Washington, Seattle, WA 98195, USA
- Suzanne Kolb
- Fred Hutchinson Cancer Research Center, Cancer Epidemiology Program, Public Health Sciences, Seattle, WA 98109, USA; Department of Epidemiology, University of Washington, School of Public Health, Seattle, WA 98195, USA
- Antonio Finelli
- Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Neil E. Fleshner
- Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Maria Komisarenko
- Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- James A. Eastham
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Behfar Ehdaie
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Nicole Benfante
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Christopher J. Logothetis
- Departments of Genitourinary Medical Oncology and Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Justin R. Gregg
- Departments of Genitourinary Medical Oncology and Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Cherie A. Perez
- Departments of Genitourinary Medical Oncology and Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Sergio Garza
- Departments of Genitourinary Medical Oncology and Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Jeri Kim
- Departments of Genitourinary Medical Oncology and Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Leonard S. Marks
- Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Merdie Delfin
- Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Danielle Barsa
- Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Danny Vesprini
- Odette Cancer Centre, Sunnybrook Health and Sciences Centre, University of Toronto, Toronto, ON, Canada
- Laurence H. Klotz
- Odette Cancer Centre, Sunnybrook Health and Sciences Centre, University of Toronto, Toronto, ON, Canada
- Andrew Loblaw
- Odette Cancer Centre, Sunnybrook Health and Sciences Centre, University of Toronto, Toronto, ON, Canada
- Alexandre Mamedov
- Odette Cancer Centre, Sunnybrook Health and Sciences Centre, University of Toronto, Toronto, ON, Canada
- S. Larry Goldenberg
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Celestia S. Higano
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Maria Spillane
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Eugenia Wu
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- H. Ballentine Carter
- Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Christian P. Pavlovich
- Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Mufaddal Mamawala
- Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Tricia Landis
- Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Peter R. Carroll
- Department of Urology, University of California, San Francisco, San Francisco, CA, USA
- June M. Chan
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA
- Matthew R. Cooperberg
- Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
- Janet E. Cowan
- Department of Urology, University of California, San Francisco, San Francisco, CA, USA
- Todd M. Morgan
- Department of Urology, University of Michigan, Ann Arbor, MI, USA
- Javed Siddiqui
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
- Rabia Martin
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
- Eric A. Klein
- Glickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
- Karen Brittain
- Glickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
- Paige Gotwald
- Glickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
- Daniel A. Barocas
- Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA
- Jeremiah R. Dallmer
- Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Jennifer B. Gordetsky
- Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Pam Steele
- Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA
- Shilajit D. Kundu
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Jazmine Stockdale
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Monique J. Roobol
- Department of Urology, Erasmus Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
- Lionne D.F. Venderbos
- Department of Urology, Erasmus Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
- Martin G. Sanda
- Department of Urology, Emory University School of Medicine, Atlanta, GA, USA
- Rebecca Arnold
- Department of Urology, Emory University School of Medicine, Atlanta, GA, USA
- Dattatraya Patil
- Department of Urology, Emory University School of Medicine, Atlanta, GA, USA
- Christopher P. Evans
- Department of Urologic Surgery, University of California, Davis Medical Center, Sacramento, CA, USA
- Marc A. Dall’Era
- Department of Urologic Surgery, University of California, Davis Medical Center, Sacramento, CA, USA
- Anjali Vij
- Department of Urologic Surgery, University of California, Davis Medical Center, Sacramento, CA, USA
- Anthony J. Costello
- Department of Urology, Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia
- Ken Chow
- Department of Urology, Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia
- Niall M. Corcoran
- Department of Urology, Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia
- Soroush Rais-Bahrami
- Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
- Courtney Phares
- Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA
- Douglas S. Scherr
- Department of Urology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
- Thomas Flynn
- Department of Urology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
- R. Jeffrey Karnes
- Mayo Clinic Department of Urology, Rochester, MN, USA
- Michael Koch
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
- Courtney Rose Dhondt
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
- Joel B. Nelson
- Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Dawn McBride
- Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Michael S. Cookson
- Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Kelly L. Stratton
- Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephen Farriester
- Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Erin Hemken
- Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Walter M. Stadler
- University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
- Tuula Pera
- University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
- Deimante Banionyte
- University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
- Fernando J. Bianco, Jr.
- Urological Research Network, Miami Lakes, FL, USA
- Isabel H. Lopez
- Urological Research Network, Miami Lakes, FL, USA
- Stacy Loeb
- Departments of Urology and Population Health, New York University Langone Health and Manhattan Veterans Affairs Medical Center, New York, NY, USA
- Samir S. Taneja
- Departments of Urology and Population Health, New York University Langone Health and Manhattan Veterans Affairs Medical Center, New York, NY, USA
- Nataliya Byrne
- Departments of Urology and Population Health, New York University Langone Health and Manhattan Veterans Affairs Medical Center, New York, NY, USA
- Christopher L. Amling
- Department of Urology, Oregon Health and Science University, Portland, OR, USA
- Ann Martinez
- Department of Urology, Oregon Health and Science University, Portland, OR, USA
- Luc Boileau
- Department of Urology, Oregon Health and Science University, Portland, OR, USA
- Franklin D. Gaylis
- Genesis Healthcare Partners, Department of Urology, University of California, San Diego, CA, USA
- Jacqueline Petkewicz
- Division of Urology, NorthShore University Health System, Evanston, IL, USA
- Nicholas Kirwen
- Division of Urology, NorthShore University Health System, Evanston, IL, USA
- Brian T. Helfand
- Division of Urology, NorthShore University Health System, Evanston, IL, USA
- Jianfeng Xu
- Division of Urology, NorthShore University Health System, Evanston, IL, USA
- Denise M. Scholtens
- Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- William J. Catalona
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- John S. Witte
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Departments of Epidemiology and Population Health, Biomedical Data Science, and Genetics, Stanford University, Stanford, CA, USA; Corresponding author
- Journal volume & issue
-
Vol. 3,
no. 1
p. 100070
Abstract
Summary: Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC.
