Abstract
DNA repair gene mutations are present in 8-10% of localized prostate cancers. It is unknown whether this is influenced by clinicopathologic factors. We interrogated localized prostate adenocarcinomas with tumor DNA sequencing information from the TCGA validated (n = 333) and Nature Genetics (n = 377) datasets. Homologous recombination repair genes included in our analysis were: ATM, BRCA1/2, CDK12, CHEK1/2, FANCA, FANCD2, FANCL, GEN1, NBN, PALB2, RAD51, and RAD51C. Proportions of cases with pathogenic DNA repair mutations (and in ATM/BRCA1/2 specifically) were reported by Gleason grade group, clinical T, pathologic T, and pathologic N stage. Odds ratios and Fisher's exact tests were used to compare proportions between categories. Patients with Gleason grade groups 3 and higher were 2.2 times more likely to harbor any DNA repair mutation (95% CI: 1.2-4.2; 10.3% versus 5.0%) and were 2.7 times more likely to have BRCA1/2 or ATM mutations (95% CI: 1.3-6.6; 7.0% versus 2.7%) compared to those in Gleason grade groups 1-2. Patients with pathologic T3 and T4 stage (pT3/pT4) were 2.6 times more likely to have any DNA repair mutation (95% CI: 1.3-6.6; 13.0% versus 5.5%) and were 3.2 times more likely to have BRCA1/2 or ATM mutations (95...Continue Reading
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