Neighborhood deprivation and risk of mortality among men with prostate cancer: Findings from a long-term follow-up study

Background: The overall survival rate of prostate cancer (PCa) has improved over the past decades. However, huge socioeconomic and racial disparities in overall and prostate cancer-specific mortality exist. The neighborhood-level factors including socioeconomic disadvantage and lack of access to care may contribute to disparities in cancer mortality. This study examines the impact of neighborhood deprivation on mortality among PCa survivors. Methods: North Carolina–Louisiana Prostate Cancer Project (PCaP) data were used. A total of 2113 men, 1046 AA and 1067 EA, with PCa were included in the analysis. Neighborhood deprivation was measured by the Area Deprivation Index (ADI) at the census block group level using data from the US Census Bureau. Quintiles of ADI were created. Cox proportional hazards and competing risk models with mixed effects were performed to estimate the effect of neighborhood deprivation on all-cause and PCa-specific mortality adjusted for age, race, study site, insurance status, and comorbidities. Results: Participants living in the most deprived neighborhoods had an increased risk for all-cause mortality (quintiles 4 + 5: adjusted hazard ratio [aHR] = 1.51, 95% confidence interval [CI] = 1.16–1.96) compared to those in the least deprived (quintile 1) neighborhoods. The risk of prostate cancer-specific mortality was also higher among those living in the deprived neighborhoods (quintiles 4 + 5: aHR = 1.90, 95% CI = 1.10–3.50) than those in the least deprived neighborhood. Conclusions: The findings suggest neighborhood-level resources or health interventions are essential to improve survival among men with PCa. Additional research should focus on the mechanisms of how the neighborhood environment affects mortality

Prostate cancer aggressiveness and financial toxicity among prostate cancer patients

Introduction: Financial toxicity (FT) is a growing concern among cancer survivors that adversely affects the quality of life and survival. Individuals diagnosed with aggressive cancers are often at a greater risk of experiencing FT. The objectives of this study were to estimate FT among prostate cancer (PCa) survivors after 10−15 years of diagnosis, assess the relationship between PCa aggressiveness at diagnosis and FT, and examine whether current cancer treatment status mediates the relationship between PCa aggressiveness and FT. Methods: PCa patients enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were recontacted for long-term follow-up. The prevalence of FT in the PCaP cohort was estimated. FT was estimated using the COmprehensive Score for Financial Toxicity, a validated measure of FT. The direct effect of PCa aggressiveness and an indirect effect through current cancer treatment on FT was examined using causal mediation analysis. Results: More than one-third of PCa patients reported experiencing FT. PCa aggressiveness was significantly independently associated with high FT; high aggressive PCa at diagnosis had more than twice the risk of experiencing FT than those with low or intermediate aggressive PCa (adjusted odds ratio [aOR] = 2.13, 95% CI = 1.14−3.96). The proportion of the effect of PCa aggressiveness on FT, mediated by treatment status, was 10%, however, the adjusted odds ratio did not indicate significant evidence of mediation by treatment status (aOR = 1.05, 95% CI = 0.95−1.20). Conclusions: Aggressive PCa was associated with high FT. Future studies should collect more information about the characteristics of men with high FT and identify additional risk factors of FT

Enhancing discovery of genetic variants for posttraumatic stress disorder through integration of quantitative phenotypes and trauma exposure information

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.</p