Researchers say they have identified genes that should be considered for gene panel testing in prostate cancer.
The researchers found evidence to suggest that variants in BRCA2, ATM, NBN, MSH2, XRCC2, and MRE11A are associated with aggressive prostate cancer. These findings were published in JAMA Oncology.
For this study, researchers performed 2-stage exome sequencing on 17,546 men of European ancestry from 18 international studies. The cohort included 8361 patients with nonaggressive prostate cancer and 9185 patients with aggressive prostate cancer (including 2397 with metastatic disease).
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The researchers conducted exome-wide sequencing and focused sequencing on 29 DNA repair pathway and cancer susceptibility genes, many of which are included in gene panels.
The researchers found the strongest evidence to suggest that variants in BRCA2, ATM, and NBN are associated with an increased risk of aggressive prostate cancer.
The frequency of deleterious BRCA2 alleles was 0.7% in patients with nonaggressive disease, 2.4% in patients with aggressive disease (odds ratio [OR], 4.29; 95% CI, 3.15-5.86; P =4.0 × 10−20), and 3.0% in patients with metastatic disease (OR, 5.61; 95% CI, 3.73-8.44; P =1.3 × 10−16).
The frequency of deleterious ATM alleles was 0.7% in patients with nonaggressive disease, 1.6% in patients with aggressive disease (OR, 2.17; 95% CI, 1.58-2.99; P =1.6 × 10−6), and 1.9% in patients with metastatic disease (OR, 2.80; 95% CI, 1.83-4.29; P =1.9 × 10−6).
The frequency of deleterious NBN alleles was 0.2% in patients with nonaggressive disease and 0.5% in patients with metastatic disease (OR, 5.16; 95% CI, 2.19-12.12; P =1.7 × 10−4).
The researchers found nominal evidence to suggest associations between aggressive prostate cancer and variants in MSH2 (OR, 3.27; 95% CI, 1.29-8.31; P =.01) and XRCC2 (OR, 6.24; 95% CI, 1.24-31.4; P =.03). The team also found a nominal association between variants in MRE11A and metastatic prostate cancer (OR, 4.70; 95% CI, 1.39-15.90; P =.01).
There was evidence to suggest potential associations between aggressive disease and variants in 5 additional genes — TP53, RAD51D, BARD1, GEN1, and SLX4 — but these associations did not reach statistical significance.
“The findings of this genetic association study implicate genes to be considered for gene panel testing in PCa [prostate cancer] that would be beneficial to a broad group of men, including those diagnosed at any stage of the disease,” the researchers wrote. “Additional large-scale sequencing studies, particularly in diverse populations, are needed to confirm the involvement or lack thereof of the genes lacking strong statistical evidence reported here.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Darst BF, Saunders E, Dadaev T, et al. Germline sequencing analysis to inform clinical gene panel testing for aggressive prostate cancer. JAMA Oncol. Published online September 21, 2023. doi:10.1001/jamaoncol.2023.3482.
This article originally appeared on Cancer Therapy Advisor