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Helen Diller Family Comprehensive Cancer Center

Largest-Ever Study of Prostate Cancer Genomics in Black Men IDs Potential Targets for Precision Therapies

Black Patients Should Also Benefit from Recently Approved PARP Inhibitor Therapies "If Applied Equitably," Study Finds

By Nicholas Weiler | UCSF.edu | July 10, 2020

Largest-Ever Study of Prostate Cancer Genomics in Black Men IDs Potential Targets for Precision Therapies

Black men in the United States are known to suffer disproportionately from prostate cancer, but few studies have investigated whether genetic differences in prostate tumors could have anything to do with these health disparities.

Franklin Huang

Franklin W. Huang, MD, PhD Assistant Professor, Department of Medicine, UCSF, and corresponding author of this study.

Now, in the largest study of its kind to date, researchers from Boston University School of Medicine (BUSM), UC San Francisco (UCSF), and Northwestern University have identified genes that are more frequently altered in prostate tumors from men of African ancestry compared to other racial groups, though the reasons for these differences is not known, the authors say. None of the individual tumor genetic differences that were identified are likely to explain significant differences in health outcomes or to prevent Black Americans from benefiting from a new generation of precision prostate cancer therapies, the authors say, as long as the therapies are applied equitably.

The newly identified gene variants could potentially lead to precision prostate cancer therapies specifically focused on men of African ancestry, and will inform broader efforts by the National Cancer Institute’s RESPOND study to link gene variants to health outcomes in an even larger cohort of Black patients nationwide.

Despite declines in mortality related to cancer in the U.S., disparities by race have persisted. One in every six Black Americans will be diagnosed with prostate cancer in their lifetime, and these men are twice as likely to die from the disease as men of other races. But it is not yet clear to researchers whether differences in prostate cancer genetics contribute to these health disparities in addition to the social and environmental inequities known to drive poorer health outcomes across the board.

To date, studies trying to figure out what genes are commonly mutated in prostate cancers often have had very few samples from racial/ethnic minority groups despite the greater burden of prostate cancer in these populations. In May, the FDA approved a class of drugs known as PARP inhibitors as a therapy for men with prostate cancers driven by specific genetic mutations, but it is not known how prevalent these mutations are in people of African descent. As more genetic health studies are performed in minority populations, it has become clear that other genetically targeted therapies that have been developed based on studies of patients of European descent are at times much less effective, and in some cases cause dangerous side-effects, in other racial and ethnic groups.

In the new study, published July 10, 2020 in Clinical Cancer Research, a journal of the American Association for Cancer Research, the research team set out to better understand differences in the mutations driving prostate cancer tumors in men with African versus European ancestry, and whether any such differences could influence disease outcomes or the effectiveness of PARP inhibitors or other targeted therapies.

The researchers collected and analyzed DNA sequencing data from previously published studies and from a commercial molecular diagnostics company. In total, they examined mutational patterns in prostate cancers from more than 600 Black men, representing the largest such study of this population to date.

The team found that the frequency of mutations in DNA repair genes and other genes that are targets of current therapeutics are similar between the two groups, suggesting that at least these classes of current precision prostate cancer therapies should be beneficial in people of both African and European ancestry, according to corresponding author Franklin Huang, MD, PhD, an assistant professor in UCSF’s Division of Hematology/Oncology and member of the UCSF Helen Diller Family Comprehensive Cancer CenterUCSF Institute for Human Genetics, and UCSF Bakar Computational Health Sciences Institute.

 

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