Links Between Ancestry, Immunogenomic Landscape Investigated in Prostate Cancer

A comparison of prostate cancer somatic copy number alterations (sCNA) and tumor immune content in Black patients and White patients with prostate cancer shows apparent links between genetic ancestry and tumor characteristics.

Writing in JCI Insight, study authors noted that Black men in the United States are more than twice as likely to die from prostate cancer than White men. That difference is likely due to multiple factors, they said, including access to care. However, they also noted that fewer Black patients have undergone immunogenic profiling. What profiling has taken place suggests there may be significant genomic and tumor immune microenvironment (TME) differences between Black and White men.

“Though sCNA prevail over mutations as the most common genomic alteration in prostate cancer and may be linked to changes in the immune TME, few prior studies have systematically compared the copy number and immune landscapes of primary prostate cancers using diverse and grade-matched cohorts,” the authors said.

In the new study, they recruited 145 self-identified Black participants and 145 self-identified White participants, all of whom had surgically treated prostate cancer. The participants were matched by Gleason grade group, and findings were adjusted for preoperative prostate-specific antigen (PSA) and age.

The investigators found 143 loci where the copy number was significantly tied to percentage of African ancestry. Those variances were clustered on chromosomes 6p, 10q, 11p, 12p, and 17p, they said.

“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,” they said.

They also found that regulatory T-cell (Treg) density in Black and White patients was closely correlated with the percentage of a patient’s genome that was altered.

“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,” the authors said.

They noted some limitations to their findings. First, they said it was not possible to obtain germline blood or saliva samples, given the long interval between patients’ treatment and this analysis.

“The lack of these data precluded germline normalization on a case-by-case basis, and we instead used a pooled subset of normal prostate tissues for normalization and a large race-matched cohort of normal colon tissue samples for filtering for gCNV [germline copy number variation],” they wrote.

The authors said there is no known evidence that tumor-specific gCNV might affect the colon but not the prostate, but they said they cannot exclude that possibility. They also noted that this was a single-center, single-region study, among other limitations. Still, they said their study amounts to a first-of-its-kind comparison.

“After extensive validation, we provide the first comprehensive mapping to our knowledge of genomic loci where loss or gain is associated with genetic ancestry, and we demonstrate that the global sCNA burden of prostate tumors does not vary by ancestry,” they said.

Reference

Vidotto T, Imada EL, Faisal F, et al. Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer. JCI Insight. Published online February 8, 2023. doi:10.1172/jci.insight.162409