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Germline inherited genes with possible treatment ramifications in metastatic prostate cancer

Germline inherited genes with possible treatment ramifications in metastatic prostate cancer
Gene Association with increased prostate cancer risk Association with other cancer risk (eg, breast, ovary, colon, uterus) and management options Prevalence of germline mutations in metastatic prostate cancer Prevalence of germline mutations in prostate cancer with family history Treatment implications in metastatic prostate cancer
Eligible for DNA-damaging agents: PARP inhibitor, platinum Eligible for immunotherapy: PD-1 inhibitor
ATM X X 1.6% 2.0% X  
BARD1         X  
BRCA1 X X 0.9% 0.7% XX  
BRCA2 X X 5.4% 4.7% XX  
BRIP1         X  
CDK12         X  
CHEK1         X  
CHEK2 X X 1.9% 2.9% X  
FANCL         X  
HOXB13 X   Not evaluated 1.1%    
MLH1 X X   0.1%   X
MSH2 X X 0.1% 0.7%   X
MSH6 X X 0.1% 0.5%   X
NBN   X 0.3% 0.3% X  
PALB2   X 0.4% 0.6% X  
PMS2 X X 0.3% 0.5%   X
RAD51B         X  
RAD51C   X 0.1% 0.2% X  
RAD51D   X 0.4% 0.2% X  
RAD54L         X  
In the column entitled Eligible for DNA damaging agents: PARP inhibitor, platinum: XX denotes those pathogenic variants that have FDA approval for rucaparib and olaparib; X denotes FDA approval for olaparib.
PARP: poly-adenosine diphosphate-ribose polymerase; PD-1: programmed cell death 1; ATM: ataxia telangiectasia mutated; BARD1: BRCA1-associated RING domain 1; BRCA: breast cancer susceptibility gene; BRIP: BRCA1-interacting protein c-terminal helicase-1; CDK: cyclin-dependent kinase; CHEK: checkpoint kinase; HOXB13: homeobox B13; MLH1: mutL homolog 1; MSH: mutS homolog; NBN: nibrin; PALB2: partner and localizer of BRCA2; PMS2: postmeiotic segregation increased 2; RAD: recombination protein A; FDA: US Food and Drug Administration.
Adapted with permission of Harborside Press, from Cheng HH, Sokolova AO, Schaeffer EM, et al. Germline and Somatic Mutations in Prostate Cancer for the Clinician. J Natl Compr Canc Netw 2019; 17:515; permission conveyed through Copyright Clearance Center, Inc.
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