The largest coordinated research effort to study biological and non-biological factors associated with aggressive prostate cancer in African-American men has begun. The $26.5 million study is called RESPOND, or Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Tumor Markers, and Social Stress. It will investigate environmental and genetic factors related to aggressiveness of prostate cancer in African-American men to better understand why they disproportionally experience aggressive disease—that is, disease that grows and spreads quickly—compared with men of other racial and ethnic groups.

RESPOND is supported by the National Cancer Institute (NCI) and the National Institute on Minority Health and Health Disparities (NIMHD), both parts of the National Institutes of Health, as well as by the Prostate Cancer Foundation (PCF). The NCI funding will be provided from the 21st Century Cures Cancer Moonshot Initiative.

“Understanding why African-American men are more likely to be diagnosed with aggressive prostate cancer than men of other racial and ethnic groups is a critical, unanswered question in cancer disparities research,” said NCI Director Ned Sharpless, MD. “This large, collaborative study can help the cancer research community better understand and address these disparities.”

African-American men have about a 15% chance of developing prostate cancer in their lifetimes, compared to about a 10% chance for white men, and African-American men are more likely to be diagnosed with aggressive disease. In addition, the risk of dying from prostate cancer for African-American men is about 4% compared to about 2% for white men. With the RESPOND study, researchers aim to learn more about why these disparities exist.

“This study, which is combining state-of-the-art molecular approaches with social and environmental science, will help unravel the complex interactions of biological, behavioral, and environmental factors that contribute to excess prostate cancer burden and poorer outcomes in African-American men, allowing development of tailored approaches for prevention, diagnosis, and treatment in this population,” said NIMHD Director Eliseo Pérez-Stable, MD.

The investigators aim to enroll 10,000 African-American men with prostate cancer into the RESPOND study. The participants will be identified primarily via NCI’s Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Disease Control and Prevention’s National Program of Cancer Registries. In addition, this study builds on years of research collaboration involving investigators who are part of the African Ancestry Prostate Cancer (AAPC) consortium. These investigators will contribute additional information and samples from 10,000 African-American men with prostate cancer. In accordance with NIH data sharing policies, and with appropriate informed consent, the de-identified data and samples collected as part of this research will be made available as a resource to the scientific community, aiding future research.

Investigators in the study will examine possible associations between aggressive disease and exposures to neighborhood/environmental stressors, such as discrimination, early-life adversity, and segregation. They will also study DNA and tumor samples to identify gene variants associated with aggressive prostate cancer. Once researchers have identified genetic changes associated with aggressive prostate cancer, they will investigate how the social environment interacts with those genetic changes.

“Previous research on prostate cancer disparities has investigated social and genetic factors separately, but we know these components interact with each other to contribute to disparities,” said Damali Martin, PhD, program director for the study in NCI’s Epidemiology and Genomics Research Program. “The ability to integrate genetic and environmental factors, including individual, neighborhood, and societal factors, into one large study will enable us to have a better understanding of how all of these factors contribute to the aggressiveness of prostate cancer.”

RESPOND, a cooperative agreement, will be led by Christopher Haiman, ScD, of the University of Southern California (USC) in Los Angeles, in collaboration with John Carpten, PhD, Ann Hamilton, PhD, and David Conti, PhD, also of USC; Scarlett Gomez, PhD, of the University of California, San Francisco; Tamara Lotan, MD, of Johns Hopkins University in Baltimore; and Franklin Huang, MD, PhD, of Dana-Farber Cancer Institute in Boston.

NCI’s Division of Cancer Epidemiology and Genetics will perform genotyping, and the Center for Inherited Disease Research at Johns Hopkins University will conduct DNA sequencing for the genetic component of the study. NCI’s Division of Cancer Control and Population Sciences is administering the study grant.

“No group in the world is hit harder by prostate cancer than men of African descent, and, to date, little is known about the biological reasons for these disparities, or the full impact of environmental factors,” said Jonathan W. Simons, MD, PCF’s president and CEO. “We celebrate our partnership and applaud NIH for spearheading this study, which we believe will help pave the way for groundbreaking discoveries that will improve health equity for African-American men and their families.”