scholarly journals Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Walter Rayford ◽  
Alp Tuna Beksac ◽  
Jordan Alger ◽  
Mohammed Alshalalfa ◽  
Mohsen Ahmed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Molecular Subtype ◽  
European American ◽  
Beta Catenin ◽  
Expression Of Genes ◽  
Repair Genes ◽  
Clinical Genomic ◽  
Lower Expression

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.

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

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.

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

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.

Variant Base Excision Repair Genes (hOGG1, APE1, XRCC1) and Prostate Cancer Risk in African‐American Men

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Daya Shankar Srivastava ◽  
Oyeyemi Komolafe ◽  
Tiva Templeton ◽  
J. Christopher States ◽  
Guy Brock ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Cancer Risk ◽  
Base Excision Repair ◽  
African American Men ◽  
Excision Repair ◽  
Prostate Cancer Risk ◽  
Base Excision ◽  
Repair Genes

Germline mutations in DNA damage repair genes and HOXB13 among African American men diagnosed with early-onset prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10505-10505
Author(s):  
Jennifer Lynn Beebe-Dimmer ◽  
Christopher Sample ◽  
Tara Baird ◽  
Azita Sadeghpour ◽  
Julie J. Ruterbusch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
African American ◽  
Family History ◽  
High Risk ◽  
Early Onset ◽  
African American Men ◽  
Damage Repair ◽  
High Risk Disease ◽  
Repair Genes

10505 Background: Inherited defects in DNA damage repair (DDR) genes (e.g. ATM, BRCA1/2) and the tumor suppresser gene HOXB13 are rare in the general population, but have been observed at a higher rate among men with early-onset and advanced prostate cancer. However, most studies include few, if any, African American men, highlighting the need to understand the contribution of mutations in these genes in this high-risk population. Methods: A population-based cohort of 757 African American men diagnosed with prostate cancer at age 62 years or younger were identified and enrolled through the Metropolitan Detroit Cancer Surveillance System (MDCSS), one of NCI’s founding members of the SEER program. Participants completed a short survey to collect information on family history, medical history (including cancer-related treatment), surveillance, and health behaviors. Each participant submitted a saliva or blood sample for genetic analyses and consent for tumor tissue if available. All clinical data were collected through linkage with the MDCSS registry. Full exome sequencing was performed and herein, we report the mutation patterns observed in a panel of DNA repair genes and HOXB13. All variants were ranked according to frequency (MAF < 1%); REVEL, SIFT and PolyPhen scores for pathogenic potential; evidence from existing literature; and prevalence in the cohort. Results: Among the 744 African American prostate cancer cases with adequate DNA for sequencing and thus included in this analysis, the mean age at diagnosis was 55.6 years, 29% reported a family history of prostate cancer in a first degree family member, and 40% were initially diagnosed with intermediate- to high-risk disease (stage T3/T4 and/or Gleason 4+3 and higher at diagnosis). We identified 20 variants that were either known or predicted to be pathogenic in 11 candidate genes ( ATM, ATR, BRCA1/2, BRIP1, CHEK2, FANCA, HOXB13, MSH2, PALB2, and PMS2). These particular variants were more common among men diagnosed before age 55 and in men with high grade cancer in this cohort. Conclusions: Our results suggest that mutations in DDR genes and HOXB13 may be important cancer risk factors for African American men diagnosed with early-onset and intermediate- to high-risk disease. Further study is necessary to describe the spectrum and prevalence of genetic mutations in this population including the characterization of variants of unknown significance.

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