PROSTATE cancer is the most commonly diagnosed, and leading cause of cancer deaths, in males in the USA. A recent study from researchers collaborating between the University of Maryland School of Medicine, USA and Virginia Commonwealth University, USA, has linked neighbourhood disadvantage to higher risks of stress-related gene expression in prostate tumours.
In this cross-sectional study, data was analysed from 218 patients who had undergone radical prostatectomy between August 1992 and January 2021. Of the 218 participants, 168 were African American males and 50 were White males.
RNA was extracted from prostate tumour tissue and analysed for expression of 105 stress-related genes. Statistical analysis involved linear regression models to evaluate the relationship between neighbourhood measures and gene expression, adjusting for race, age, and year of surgery.
The study included geocoded residential addresses at the time of diagnosis to assess neighbourhood factors through the use of the Area Deprivation Index (ADI), a custom Neighbourhood Deprivation Index, the Racial Isolation Index, and historical redlining.
The results suggest that neighbourhood disadvantage is linked to biological pathways related to stress and inflammation in prostate tumours, contributing to cancer disparities. African American participants saw greater neighbourhood disadvantage than White participants and ADI was positively associated with the expression of 11 genes.
The study identified significant associations between neighbourhood factors and gene expression, particularly highlighting the serotonin pathway gene HTR6, which remained significant after a multiple comparisons adjustment. Additionally, the expression of five proinflammatory genes in the conserved transcriptional response to adversity was associated with greater neighbourhood disadvantage.
These results support the hypothesis that neighbourhood disadvantage influences stress-related gene expression which could increase aggressive prostate cancer risk. As the first of its kind, the study had multiple strengths including using multiple measures of neighbourhood disadvantage and comprehensive transcriptomic data, however, limitations such as small sample sizes, potential selection bias, and limited individual-level data are possible areas to be addressed in future research.
Katie Wright, EMJ
Reference
Boyle J et al. Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes. JAMA Netw Open. 2024;7(7):e2421903.
