Association of Susceptibility Alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with Prostate Cancer Severity in European American and African American Men

AbstractRacial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

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Understanding the Relationship between Environmental Arsenic and Prostate Cancer Aggressiveness among African-American and European-American Men in North Carolina

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17228364 ◽

2020 ◽

Vol 17 (22) ◽

pp. 8364

Author(s):

Humberto Parada ◽

Tianying Wu ◽

Rebecca C. Fry ◽

Laura Farnan ◽

Gary J. Smith ◽

...

Keyword(s):

Prostate Cancer ◽

North Carolina ◽

African American ◽

African American Men ◽

European American ◽

Total Arsenic ◽

Cross Sectional ◽

Low Level ◽

Cancer Aggressiveness ◽

Arsenical Species

High-level exposure to arsenic, a known carcinogen and endocrine disruptor, is associated with prostate cancer (PCa) mortality. Whether low-level exposure is associated with PCa aggressiveness remains unknown. We examined the association between urinary arsenic and PCa aggressiveness among men in North Carolina. This cross-sectional study included 463 African-American and 491 European-American men with newly diagnosed, histologically confirmed prostate adenocarcinoma. PCa aggressiveness was defined as low aggressive (Gleason score < 7, stage = cT1–cT2, and PSA < 10 ng/mL) versus intermediate/high aggressive (all other cases). Total arsenic and arsenical species (inorganic arsenic (iAsIII + iAsV), arsenobetaine, monomethyl arsenic, and dimethyl arsenic)) and specific gravity were measured in spot urine samples obtained an average of 23.7 weeks after diagnosis. Multivariable logistic regression was used to estimate the covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for PCa aggressiveness in association with arsenic tertiles/quantiles overall and by race. The highest (vs. lowest) tertile of total arsenic was associated with PCa aggressiveness ORs of 1.77 (95% CI = 1.05–2.98) among European-American men, and 0.94 (95% CI = 0.57–1.56) among African-American men (PInteraction = 0.04). In contrast, total arsenic and arsenical species were not associated with PCa aggressiveness in unstratified models. Low-level arsenic exposure may be associated with PCa aggressiveness among European-Americans, but not among African-Americans.

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Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer

10.21203/rs.3.rs-668276/v1 ◽

2021 ◽

Author(s):

Tsion Minas ◽

Julián Candia ◽

Tiffany Dorsey ◽

Francine Baker ◽

Wei Tang ◽

...

Keyword(s):

Prostate Cancer ◽

African American ◽

Tumor Immunity ◽

African American Men ◽

African Ancestry ◽

European American ◽

Serum Proteomics ◽

Immune Oncology ◽

Lethal Prostate Cancer ◽

West African Ancestry

Abstract There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determined if men of African descent harbor a unique systemic immune-oncological signature and measured 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis were significantly elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associated with metastatic and lethal prostate cancer, pointing to clinical significance. Moreover, two markers, pleiotrophin and TNFRSF9, predicted poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.

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