Dataset Information

Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer.

ABSTRACT: The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically treated cohort of 145 self-identified Black (BL) and 145 self-identified White (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, preoperative prostate-specific antigen (PSA), and Gleason Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, preoperative PSA levels, and Gleason Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, Treg density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that Treg infiltration varies by global sCNA burden in primary disease.

SUBMITTER: Vidotto T

PROVIDER: S-EPMC9977441 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer.

Vidotto Thiago T Imada Eddie L EL Faisal Farzana F Murali Sanjana S Mendes Adrianna A AA Kaur Harsimar H Zheng Siqun S Xu Jianfeng J Schaeffer Edward M EM Isaacs William B WB Sfanos Karen S KS Marchionni Luigi L Lotan Tamara L TL

JCI insight 20230208 3

The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically treated cohort of 145 self-identified Black (BL) and 145 self-identified White (WH) patients with genetic ancestry estimation ...[more]

PMID: 36752203

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Project description:BackgroundSocioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men.ObjectiveTo compare differences in PC subtype frequency and genomic aggressiveness by self-identified race.Design setting and participantsFive molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID).Outcome measurements and statistical analysisDifferences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ2 tests and multivariable-adjusted logistic regression models.Results and limitationsSubtype frequencies differed by race for four classifiers. Subtypes characterized by the presence of SPOP mutations, SPINK1 overexpression, and neuroendocrine differentiation were more common among Black men. ERG and ETS fusion-positive subtypes were more frequent among White men, with no clear differences for subtypes reflecting luminal versus basal lineage. The hypothesized low-risk Kamoun S2 subtype was associated with a lower Decipher score among White men only (p = 0.01 for heterogeneity), while the aggressive You PCS1 subtype was associated with a higher Decipher score among White men only (p = 0.001 for heterogeneity). The Tomlins ERG+ subtype was associated with a higher Decipher score relative to all other subtypes among Black men, with no association among White men (p = 0.007 for heterogeneity).ConclusionsThe frequency of PC molecular subtypes differed by self-identified race. Additional studies are required to evaluate whether our observations suggest differences in the tumor genomic risk of progression by self-identified race.Patient summaryWe studied five classifiers that identify subtypes of prostate tumors and found that subtypes differed in frequency between Black and White patients. Further research is warranted to evaluate how differences in tumor subtypes may contribute to disparities in prostate cancer mortality.

Dataset Information

Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer.

Publications

Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer.

Similar Datasets

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