Keck School of Medicine researchers have identified a variant in the genome that may explain why multiple men in the same family develop the disease — and could serve as a guide for screening
For years, researchers have known that men of African ancestry are at greater risk of developing prostate cancer with research suggesting that inherited factors may contribute to their greater risk.
Now, a new USC study published in European Urology is the first to identify an inherited genetic variant associated with higher risk of prostate cancer in men of African descent that contributes to the clustering of prostate cancer cases within families.
“About 12% of men of African ancestry carry this particular variant in the genome, which increases their risk two-fold. The variant is not found in other populations,” said Christopher Haiman, ScD, study author and Professor of Preventive Medicine, Keck School of Medicine of USC. “But it’s even more common in families with a history of prostate cancer.”
African American men at higher risk
One in six African American men develops prostate cancer in his lifetime. African American men are 1.8 times more likely to be diagnosed with – and 2.2 times more likely to die from – prostate cancer than white men. If a black man’s brother or father had prostate cancer, his risk will be even higher. But until now, there has been no genetic mutation or biomarker doctors could look for to determine if a particular African American man was more likely to get the disease.
While a prostate specific-antigen (PSA) blood test can detect prostate cancer, many of the cancers it detects may not cause harm, while treatment can cause life-altering side effects.
In the study, which is part of the RESPOND African American prostate cancer initiative, researchers looked at 9,052 prostate cancer cases among men of African ancestry. More than 23 percent had this specific genetic variant. The variant was strongly associated with a prostate cancer diagnosis at an earlier age, more aggressive disease, and men with a family history of prostate cancer. In fact 32 percent of the men with prostate cancer who had a family history of the disease carried the variant.
Variant could aid in screening and treatment decisons
This new information may eventually help clinicians identify men who could benefit from early prostate cancer screening and treatment.
“A man of African ancestry comes in and says, ‘Well, I have prostate cancer and I have a family history of the disease. Why?.’ Well, now there’s a variant you can test to see if they and their family members carry it,” said Haiman. “This is a marker that down the road may be used to identify African-Americans and their family members who are at high risk and would benefit from more precise, targeted, and earlier PSA screening.”
Researchers believe this variant is one of the reasons why African American men are more likely to get prostate cancer and hope to find out more about the role genetic mutations play in their overall risk.
About this study
In addition to Haiman, the study’s other authors include Burcu F. Darst, Peggy Wan, Xin Sheng, Sue A. Ingles, John Carpten, Mariana C. Stern, David V. Conti, Susan M. Gundell, Loreall Pooler and Lucy Xia of the Keck School of Medicine of USC; Jeannette T. Bensen and James L. Mohler of University of North Carolina at Chapel Hill; Benjamin A. Rybicki and Christine Neslund-Dudas of Henry Ford Hospital; Barbara Nemesure and Anselm J.M. Hennis of Stony Brook University; Esther M. John of Stanford University School of Medicine; Jay H. Fowke of The University of Tennessee Health Science Center; Victoria L. Stevens and Susan M. Gapstur of the American Cancer Society; Sonja I. Berndt, Meredith Yeager and Stephen J. Chanock of the National Cancer Institute, National Institute of Health; Chad D. Huff and Sara S. Strom, of the University of Texas MD Anderson Cancer Center; Jong Y. Park, Thomas A. Sellers and Kosj Yamoah of the Moffitt Cancer Center and Research Institute; Wei Zheng, Melinda C. Aldrich, Peter E. Clark and William J. Blot of the Vanderbilt University School of Medicine; Elaine A. Ostrander of the National Human Genome Research Institute, National Institutes of Health; Patrick C. Walsh and William B. Isaacs of the Johns Hopkins Hospital and Medical Institutions; Shiv Srivastava, Gyorgy Petrovics and Jennifer Cullen of the Uniformed Services University of the Health Sciences; Adam B. Murphy of Northwestern University; Maureen Sanderson of Meharry Medical College; Dana C. Crawford and William S. Bush of Case Western Reserve University; Olivier Cussenot and Geraldine Cancel-Tassin of CeRePP; Rick A. Kittles of the City of Hope Comprehensive Cancer Center; Jianfeng Xu of the NorthShore University HealthSystem; Zsofia Kote-Jarai, Koveela Govindasami and Rosalind A. Eeles of the Institute of Cancer Research; Anand P. Chokkalingam of the University of California, Berkeley; Luc Multigner, Florence Menegaux, Pascal Blanchet and Laurent Brureau of Inserm; Marie-Elise Parent of INRS-Institut Armand-Frappier; Adam S. Kibel of the Dana-Farber Cancer Institute; Eric A. Klein of the Cleveland Clinic; Phyllis J. Goodman and Janet L. Stanford of the Fred Hutchinson Cancer Research Center; Bettina F. Drake of the Washington University School of Medicine; Jennifer J. Hu of the University of Miami Miller School of Medicine; Graham Casey of the University of Virginia; Alexander Lubwama and Stephen Watya of the Makerere University College of Health Sciences; Ian M. Thompson Jr and Robin Leach of the University of Texas Health Science Center; Elizabeth T.H. Fontham and Diptasri Mandal of Louisiana State University Health Sciences Center; Gary J. Smith of the Roswell Park Cancer Institute; Jack A. Taylor of the National Institute of Environmental Health Services; Kathleen Cooney of Duke University of Medicine.
This study was supported the National Cancer Institute at the National Institutes of Health (grants U19 CA148537, U19 CA214253, R01 CA165862, and K99 CA246063). Dr. Burcu F. Darst was supported in part by an award from the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter.