Invitae, San Francisco, CA
Piper L.W. Nicolosi , Elisa Ledet , Shan Yang , Scott T. Michalski , James Vu , A. Oliver Sartor
Background: Pathogenic DNA repair defects are well described in Caucasian (C) men with prostate cancer (PCa) but comparative data on African-American (AA) men are sparse. Methods: Germline testing for DNA repair defects were assayed by Invitae (Invitae.com). Pathogenic variants in 14 genes were compared between AA and C men with PCa; these particular genes were also assessed by Pritchard et al NEJM 375:443, 2016. Identical gene panels were not used in all men, thus variations in assay numbers from gene to gene are noted. Chi square was used to compare proportions. Results: In the 14 genes, there were 16/214 (7.5%) AA men and 347/2488 (13.9%) C men with pathogenic findings (p=0.008). As shown in the Table, the most common pathogenic variants in AA men were BRCA2 (6/214, 2.8%), BRCA1 (3/213, 1.4%), PALB2 (2/182, 1.1%), ATM (2/206, 1.0%), RAD51C (1/148, 0.68%), CHEK2 (1/207, 0.48%), and PMS2 (1/212, 0.47%). In contrast to C men in this series, no AA men had pathogenic mutations in BARD1, BRIP1, MLH1, MSH2, MSH6, NBN, or RAD51D. Pathogenic CHEK2 was less commonly detected in AA as compared to C (p=0.03) in this dataset. Comparing our C men revealed no differences in the proportion of men with pathogenic findings compared to Pritchard et al (13.9% here vs 11.8%, P=0.15). Conclusions: AA men with PCa are less likely to have pathogenic DNA repair mutations among these 14 assayed DNA repair genes compared to C men. Limitations regarding lack of stage, Gleason scores, and FH are notable. Details on gene assays and comparison to Pritchard et al NEJM 375:443, 2016
Gene | AA Men tested | % pathogenic | C men tested | % pathogenic | AA vs C P value | Pritchard tested | % pathogenic Pritchard |
---|---|---|---|---|---|---|---|
ATM | 206 | 0.97% | 2302 | 2.09% | 0.27 | 692 | 1.59% |
BARD1 | 140 | 0.00% | 1695 | 0.00% | 1.00 | 561 | 0.00% |
BRCA1 | 213 | 1.41% | 2469 | 1.17% | 0.76 | 692 | 0.87% |
BRCA2 | 214 | 2.80% | 2488 | 4.78% | 0.18 | 692 | 5.35% |
BRIP1 | 148 | 0.00% | 1779 | 0.39% | 0.44 | 561 | 0.18% |
CHEK2 | 207 | 0.48% | 2379 | 3.11% | 0.03 | 534 | 1.87% |
MLH1 | 212 | 0.00% | 2402 | 0.08% | 0.67 | 692 | 0.00% |
MSH2 | 212 | 0.00% | 2408 | 0.79% | 0.19 | 692 | 0.14% |
MSH6 | 213 | 0.00% | 2403 | 0.37% | 0.37 | 692 | 0.14% |
NBN | 200 | 0.00% | 2262 | 0.44% | 0.34 | 692 | 0.29% |
PALB2 | 182 | 1.10% | 2171 | 0.60% | 0.42 | 692 | 0.43% |
PMS2 | 212 | 0.47% | 2403 | 0.42% | 0.90 | 692 | 0.29% |
RAD51C | 148 | 0.68% | 1760 | 0.23% | 0.31 | 692 | 0.14% |
RAD51D | 162 | 0.00% | 1940 | 0.15% | 0.61 | 692 | 0.43% |
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Abstract Disclosures
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First Author: A. Oliver Sartor
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