Genetic variants linked to aggressive prostate cancer in men of African ancestry
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October 06, 2022
3 min read
Source/Disclosures
Published by:
Elhussin IA, et al. SPOP mutation is associated with higher immunogenicity in African American men compared to European American men with prostate cancer. Presented at: American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Sept. 16-19, 2022; Philadelphia.
Disclosures:
Yates reports being a shareholder in Riptide Bioscience and consultant roles for Amgen, QED Therapeutics and Riptide Bioscience.
Researchers have identified genetic variants in prostate tumors of men of African descent that appear to be associated with African ancestry.
The findings of two studies — presented during American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved — demonstrated the potential impact of ancestry on tumor biology and may have implications for the treatment of Black men of African descent, researchers noted.
Differences in genetic variants mean that patients of African descent need to be “treated with precision in mind,” according to Clayton C. Yates, PhD, senior author for both studies, director of the Center for Biomedical Research at Tuskegee University and chair of the AACR Minorities in Cancer Research Council.
“We need to go beyond looking only at certain populations when we perform genomic profiling,” Yates told Healio.
SPOP mutation
The first study used genome-wide sequencing to look for evidence of an immune inflammatory process characterized by changes in immunogenicity that increase the risk for lethal prostate cancer in Black men.
Researchers obtained whole-exome sequencing or RNA sequencing of tumor biopsy samples of 72 patients with previously untreated prostate cancer, including 16 men of African descent, 25 of European ancestry, one of Asian race and 30 with no reported race.
The investigators found men of African descent more likely to harbor the SPOP mutation, a tumor-suppression gene that has been previously associated with aggressive prostate cancer. SPOP alterations occur in approximately 10% to 15% of all prostate cancers.
The study showed the SPOP mutation in patients of African ancestry correlated with increased expression of a proinflammatory immune gene signature, with increased infiltration of immune cells into the tumor, the researchers noted.
The study results suggest the SPOP mutation is ancestrally associated and more prevalent in both African Americans and those of West African ancestry compared with those of European ancestry, Yates said.
“Our study shows that this SPOP mutation is predisposing patients of West African ancestry toward inflammatory-type prostate cancer that is more aggressive,” he added.
Shared mutations
The second study — simultaneously published in Cancer Research Communications — used whole-exome sequencing to identify genetic variants associated with prostate cancer that are shared by men of Nigerian and African American ancestry.
Researchers collected prostate biopsy samples from 45 patients of Nigerian ancestry with previously untreated prostate cancer and compared them for genetic variations against 11 unmatched noncancerous prostate tissue samples from men of African American and European American ancestry in The Cancer Genome Atlas database.
The investigators identified several genetic variants shared between prostate tumors from men of Nigerian and African American ancestry — most frequently variants in the BRCA1 DNA repair gene.
“We found specific variants of the BRCA gene linked to prostate cancer in men of West African ancestry that are not currently clinically tested for in typical genomic panels,” Yates said. “We found a novel variant that was a driver gene specific to Nigerians and a second variant common between Nigerians and African Americans that was not present in Europeans.”
Researchers also observed that patients with higher proportions of African ancestry had more frequent BRCA1 mutations, whereas those with lower proportions had fewer mutations.
Clinical implications
“These results call for an expansion of what we look for in clinical genomic panels to include these variants and other variants known to be associated with minority patients, especially those of African Americans,” Yates told Healio. “Otherwise, we will miss what we don’t see, not because it’s not there, but because we are failing to test for it.”
Recently developed immunotherapies — although a breakthrough in many other types of cancer — have been ineffective in prostate cancer, Yates said. Pathologic specimens of prostate tumors often demonstrate a paucity of immune cells within samples, he noted. They are what those in the field call immunologically “cold tumors,” he added.
“We found that patients who harbor SPOP mutations have tumors that are filled with immune cells, and these are the type of patients who have been shown to respond to immunotherapy — including immune checkpoint inhibitors,” Yates said. “We may have found a cohort of individuals who could respond to immunotherapy that was previously not used for patients with prostate cancer.”
Yates said his group is currently working with immuno-oncologists on opening a clinical trial that would evaluate the effectiveness of anti-PD-1 therapy among men of African ancestry with the SPOP variant whose prostate tumors express high levels of PD-1.
References
- Elhussin IA, et al. SPOP mutation is associated with higher immunogenicity in African American men compared to European American men with prostate cancer. Presented at: American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Sept. 16-19, 2022; Philadelphia.
- White J, et al. Cancer Res Commun. 2022;doi:10.1158/2767-9764.CRC-22-0136.
- White J, et al. Whole exome sequencing of Nigerian prostate tumors from the Prostate Cancer Transatlantic Consortium (CaPTC) reveals DNA repair genes associated with African ancestry. Presented at: American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Sept. 16-19, 2022; Philadelphia.
For more information
Clayton C. Yates, PhD, can be reached at Center for Cancer Research, Tuskegee University, Carver Research Bldg., Room 22, Tuskegee, AL 36088; email: cyates@tuskegee.edu.
Race and Medicine
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