Differences in Germline Variant Spectrum Between Black and White Men With Prostate Cancer



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In a study presented at the 2022 ASCO Annual Meeting (Abstract 10502) and simultaneously published in JCO Precision Oncology, Veda N. Giri, MD, and colleagues found that Black men with prostate cancer exhibited a lower frequency and narrower spectrum of germline pathogenic or likely pathogenic variants and a higher frequency of variants of unknown significance vs White men, including multiple variants of unknown significance in DNA repair genes.

The study included a cohort of 427 men at Thomas Jefferson University, enriched for Black men (Black = 237, White = 190), who underwent germline testing with a 14-gene panel for ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, and TP53

Key Findings

Overall, pathogenic/likely pathogenic variants were identified in 8.2% of patients, including 5.91% of Black men vs 11.05% of White men (P = .05). Factors associated with a lower likelihood of the presence of pathogenic/likely pathogenic variants included Black vs White race (odds ratio [OR] = 0.51, P = .07) and age > 50 vs ≤ 50 years (OR = 0.48, P = .06). Moreover, a narrower spectrum of pathogenic/likely pathogenic variants was found in Black men (BRCA2, PALB2, ATM, and BRCA1) compared with White men (BRCA2, ATM, HOXB13, CHEK2, TP53, and NBN).

Variants of unknown significance (25.32% vs 16.32%, P = .02) and the presence of multiple variants of unknown significance (5.1% vs 0.53%, P = .008) were significantly more common in Black men. Among Black men, multiple variants of unknown significance were exclusively in DNA repair genes, including BRCA2, BRCA1, ATM, MLH1, MSH2, and CHEK2.

The investigators concluded, “Germline evaluation in a cohort enriched for Black men highlights the narrower spectrum of germline contribution to prostate cancer with significantly higher rates of multiple variants of unknown significance in DNA repair genes. These results underscore the imperative to engage Black men in germline testing, the need for larger panel testing in Black men, and the necessity to incorporate novel genomic technologies to clarify variants of unknown significance to discern the germline contribution to prostate cancer. Furthermore, tailored genetic counseling for Black men is important to ensure understanding of variants of unknown significance and promote equitable genetics care delivery.”

Dr. Giri, of Sidney Kimmel Cancer Center, Thomas Jefferson University, is the corresponding author for the JCO Precision Oncology article.

Disclosure: The study was funded by the National Cancer Institute and Department of Defense. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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