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Neighborhood disadvantage linked to stress-related genes that may increase prostate cancer risk
Author(s):
“Our findings suggest an impact of living in disadvantaged neighborhoods—which more commonly affects African Americans—on stress-related genetic pathways in the body. We believe this may increase an individual’s risk of aggressive prostate cancer and contribute to prostate cancer disparities by race,” says Kathryn Hughes Barry, PhD, MPH.
New data published in JAMA Network Open suggest a link between living in a disadvantaged neighborhood and a higher prostate tumor RNA expression of stress-related genes in African American and White patients with prostate cancer, which may contribute to a higher risk of aggressive prostate cancer.1
ADI was found to be associated with higher RNA expression for 11 stress-related genes.
“Our findings suggest an impact of living in disadvantaged neighborhoods—which more commonly affects African Americans—on stress-related genetic pathways in the body. We believe this may increase an individual’s risk of aggressive prostate cancer and contribute to prostate cancer disparities by race,” said senior author, Kathryn Hughes Barry, PhD, MPH, in a news release on the findings.2 Barry is an assistant professor in the department of epidemiology and public health at the University of Maryland School of Medicine (UMSOM) and a cancer epidemiology researcher at the University of Maryland Greenebaum Comprehensive Cancer Center.
The cross-sectional study included tumor tissue data from a total of 218 men with prostate cancer, of whom 77% (168) were African American and 23% (50) were White. All patients included in the study underwent radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. The median age at surgery was 58 years.
Consistent with previous work, African American participants were shown to have experienced greater neighborhood disadvantage than White participants. Specifically, the median Area Deprivation Index (ADI) was 115 among African American patients vs 92 among White patients, and the median Racial Isolation Index (RI) was 0.68 among African American patients vs 0.11 among White patients.
Upon analysis, ADI was found to be associated with higher RNA expression for 11 stress-related genes. After multiple-comparison adjustment, the association with HTR6, a serotonin pathway, remained significant (β = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). According to the authors, prior work has demonstrated a link between the expression of HTR genes and lethal prostate cancer.1 The investigators also found an association between neighborhood disadvantage and higher expression of 5 proinflammatory genes, which are relevant in prostate cancer, in the Conserved Transcriptional Response to Adversity (CTRA).
However, the authors note that further study is still needed.
Barry added, “We need to conduct larger studies to investigate the interrelationships of different neighborhood factors, individual-level factors, tumor biology, tumor aggressiveness, and patient outcomes to help inform interventions to reduce prostate cancer disparities.”2
According to the news release, the team is planning to conduct a follow-up study that would include patients from other regions across the US.2
Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore, concluded in the news release, “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, such as the [CTRA], and underscores the importance of developing interventions to improve the health and well-being of our minority populations.”2
References
1. 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
2. Living in disadvantaged neighborhoods influences stress-related genes, which may contribute to aggressive prostate cancer in African American men. News release. University of Maryland Medical Center. Published online and accessed July 12, 2024. https://www.newswise.com/articles/living-in-disadvantaged-neighborhoods-influences-stress-related-genes-which-may-contribute-to-aggressive-prostate-cancer-in-african-american-men
