Germline DNA repair mutations in men with prostate cancer are less frequent in African Americans as compared with Caucasians.

Authors

null

Piper L.W. Nicolosi

Invitae, San Francisco, CA

Piper L.W. Nicolosi , Elisa Ledet , Shan Yang , Scott T. Michalski , James Vu , A. Oliver Sartor

Organizations

Invitae, San Francisco, CA, Tulane University Cancer Center, New Orleans, LA, Tulane University, New Orleans, LA, Tulane Medical School, New Orleans, LA

Research Funding

Other

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

GeneAA Men tested% pathogenicC men tested% pathogenicAA
vs C
P value
Pritchard tested% pathogenic Pritchard
ATM2060.97%23022.09%0.276921.59%
BARD11400.00%16950.00%1.005610.00%
BRCA12131.41%24691.17%0.766920.87%
BRCA22142.80%24884.78%0.186925.35%
BRIP11480.00%17790.39%0.445610.18%
CHEK22070.48%23793.11%0.035341.87%
MLH12120.00%24020.08%0.676920.00%
MSH22120.00%24080.79%0.196920.14%
MSH62130.00%24030.37%0.376920.14%
NBN2000.00%22620.44%0.346920.29%
PALB21821.10%21710.60%0.426920.43%
PMS22120.47%24030.42%0.906920.29%
RAD51C1480.68%17600.23%0.316920.14%
RAD51D1620.00%19400.15%0.616920.43%

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2019 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer,Prostate Cancer

Sub Track

Prostate Cancer - Advanced Disease

Citation

J Clin Oncol 37, 2019 (suppl 7S; abstr 258)

DOI

10.1200/JCO.2019.37.7_suppl.258

Abstract #

258

Poster Bd #

L15

Abstract Disclosures

Similar Abstracts

Abstract

2020 Genitourinary Cancers Symposium

Assessment of inherited DNA repair defects in African-American and Caucasian men with prostate cancer.

First Author: A. Oliver Sartor

First Author: Anna Couvillon

First Author: Channing Judith Paller