PALB2:
PALP2 mutation is associated with 6.3 higher risk for aggressive
PCa74. The rate of PALB2 somatic mutation is not
significantly higher between EAM (0.83%) and AAM (2.16%) with
metastatic PCa (Table 1)67. The rates of PALB2
germline mutation, on the other hand, is similar in both races with a
range from 0.43 to 0.5% in EAM and from 0 to 0.5 % in AAM with
metastatic prostate cancer (Table 2)6465.
CHEK2 :
CHEK2 is a tumor suppressor gene located on chromosome 22q and is
associated with a significantly higher prevalence in men with metastatic
PCa compared with localized PCa. CHEK2 encodes a cell cycle checkpoint
protein kinase that plays a role in the regulation of tumor protein 53
(TP53) and DNA repair. The rates of CHEK2 somatic mutations is 2.32% in
EAM and 1.08% in AAM (Table 1)67. The studies
reported CHEK2 germline mutation range from 1.01-2% in EAM and 0%
germline mutation rate in the AAM (Table 2)6465.
Lynch syndrome:
Lynch syndrome is an inherited cancer predisposition syndrome with an
increased risk of numerous malignancies, doubling the risk of PCa. It is
caused by germline mutations in the mismatch repair genes MLH1, MSH2,
MSH6 and PMS275. The included studies show a rate of
somatic mutations in the EAM population ranging from 1.30-1.76%. The
AAM population presents a similar expression rate with a range that
varies from 1.08-1.62% (Table 1)67. Regarding
germline mutations, the EAM population presented a range from
0.14-0.70%, while the AAM population presented a range from 0.0-1.80%
(Table 2)64 65 71.
NBN :
NBN encodes for Nibrin a protein within the Mre11-RAD50-NBS1
double-stranded DNA break repair complex. NBN is a newly emerged gene
that is identified as PCa-susceptibile76. For the NBN
mutation, the included studies presented a somatic mutation rate of
0.65% in EAM, while the AAM population presented a rate of 1.08%
(Table 1)67. The EAM population presented a germline
mutation rate of 0.0-1% while the AAM population has an NBN germline
mutation rate of 0.0-0.9%(Table 2)6465 71.