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Comparing the tumours of 2,069 men treated at one hospital found real genomic differences by race that survived adjusting for stage and PSA, including more of the chromosome change that carries the worst prognosis in Black men.
Among 2,069 men with prostate cancer with access to clinical-grade sequencing at the same cancer centre, 1,841 self-reported White, 63 Asian and 165 Black, the prevalence of tumour and germline alterations was assessed in driver genes previously reported to differ by race. Clinical characteristics including PSA, age at diagnosis and cancer stage at sample procurement differed by self-reported race, but most genomic differences persisted after adjustment. Tumours from Black men carried fewer PTEN mutations and more AR alterations than those from White men; tumours from Asian men carried more FOXA1 mutations and more ZFHX3 alterations. Despite fewer TP53 mutations, tumours from Black men had more aneuploidy, particularly gains of chromosome arm 8q, an adverse prognostic factor. Genetic ancestry was associated with similar tumour alterations to self-reported race but also with modifiable cancer risk factors, and community-level average income was associated with 8q gain after adjusting for race and ancestry.
It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.
Shares Copy number alteration (CNA), Prostate cancer (KEGG map), Chromosomal instability & aneuploidy, Androgen receptor signalling.
Shares Copy number alteration (CNA), PTEN, Chromosomal instability & aneuploidy, Clinical Cancer Research.
Shares FOXA1, Prostate cancer (KEGG map), Androgen receptor signalling, Driver mutation.
Shares PTEN, Androgen receptor signalling, Driver mutation, Androgen receptor.
Shares Clinical Cancer Research, Androgen receptor signalling, Driver mutation, Androgen receptor.
Shares Copy number alteration (CNA), Chromosomal instability & aneuploidy, Androgen receptor signalling, Androgen receptor.
Shares Prostate cancer (KEGG map), Androgen receptor signalling, Driver mutation, Androgen receptor.
Shares Androgen receptor signalling, Driver mutation, Androgen receptor, Comprehensive genomic profiling.