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  • seqadmin
    Senior Member
    • Oct 2022
    • 729

    #1

    Stress-Related Gene Activity Higher in Disadvantaged Neighborhoods Linked to Aggressive Prostate Cancer

    Recent research indicates that individuals residing in disadvantaged neighborhoods exhibit significantly elevated activity of stress-related genes, potentially contributing to higher rates of aggressive prostate cancer among African American men. This study, jointly led by the University of Maryland School of Medicine (UMSOM) and Virginia Commonwealth University (VCU), was published in JAMA Network Open.

    Disparities in Prostate Cancer Rates
    African American men face a higher incidence of prostate cancer and are more than twice as likely to die from the disease compared to White men in the U.S. Often diagnosed with aggressive cancer at an earlier age, the reasons behind these disparities remain elusive.

    "Our findings suggest an impact of living in disadvantaged neighborhoods—which more commonly affects African Americans—on stress-related genetic pathways in the body," said Kathryn Hughes Barry, PhD, MPH, Assistant Professor in the Department of Epidemiology and Public Health at UMSOM and a cancer epidemiology researcher at the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC). "We believe this may increase an individual’s risk of aggressive prostate cancer and contribute to prostate cancer disparities by race."

    Genetic Expression and Cancer Risk
    The study identified a significant association between neighborhood disadvantage and higher expression of stress-related genes. Extreme hardships or trauma can influence gene expression in DNA, triggering a series of events that may lead to cancer or other adverse health outcomes.

    Among the genes with increased expression, five were related to inflammation, a factor pertinent to prostate cancer and other health conditions. The gene HTR6, part of the serotonin pathway, exhibited the strongest link. This pathway facilitates communication between the brain and other body parts and helps regulate the immune response. Various HTR genes have been associated with lethal prostate cancer.

    This observational study analyzed 105 stress-related genes from over 200 African American and White men with prostate cancer, Barry noted. It is among the first to suggest a potential link between neighborhood socioeconomic factors and RNA expression in prostate tumors.

    Methodology
    The research team examined tumor tissue from 218 men with prostate cancer who underwent radical prostatectomy at the University of Maryland Medical Center (UMMC) from 1992 to 2021. Of these, 168 were African American, and 50 were White.

    Researchers assessed neighborhoods where patients lived at the time of diagnosis using two indexes that measured neighborhood deprivation, considering income, education, employment, and housing quality. They also examined racial segregation and historical redlining, noting that neighborhoods affected by redlining in the 1930s still exhibit higher disadvantage and worse health outcomes, including cancer, today.

    "The findings from our study support and build on existing research on the emerging importance of neighborhood factors and chronic stress to better understand aggressive prostate cancer and persistent racial disparities," said Joseph Boyle, PhD, the study's first author and a postdoctoral research fellow and biostatistician at the Massey Comprehensive Cancer Center at VCU.

    Future Research Directions
    Barry emphasized the need for larger studies to explore the interrelationships of neighborhood factors, individual-level factors, tumor biology, tumor aggressiveness, and patient outcomes to inform interventions aimed at reducing prostate cancer disparities. She and her colleagues plan a broader follow-up study incorporating data from patients across different U.S. regions.

    Mark T. Gladwin, MD, Dean of UMSOM, commented on the broader implications: "The research reveals a complex interplay between environment and genes, which is becoming increasingly important in the study of cancer health disparities. It provides support for a potentially harmful effect of living in economically disadvantaged communities on stress-related genetic signaling pathways and underscores the importance of developing interventions to improve the health and well-being of our minority populations."

    Original Publication
    Boyle J, Yau J, Slade JL, et al. Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes. JAMA Netw Open. 2024;7(7):e2421903. doi:10.1001/jamanetworkopen.2024.21903


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