743 844
found in 11 lethal PCa patients (3.51%) and four localized
PCa patients (0.82%),
p
= 0.013. For
ATM
, mutations were
found in six lethal PCa patients (1.92%) and two localized
PCa patients (0.41%),
p
= 0.06. For
BRCA1
, mutations were
found in two lethal PCa patients (0.64%) and one localized
PCa patient (0.41%),
p
0.99. The higher mutation
frequency in lethal PCa compared with localized PCa
patients was observed in all three racial groups. The
difference was particularly striking in Chinese patients
where three
BRCA2
mutations and one
ATM
mutation were
found in 22 lethal PCa patients (18.18%) while none were
found in 45 localized PCa patients,
p
= 0.0095. No patients in
[(Fig._1)TD$FIG]
Fig. 1 – Germline pathogenic and likely pathogenic mutations in
BRCA1/2
and
ATM
. Each mutation (complementary DNA position and resulting amino
acid change) found in these three genes is presented by a lollipop plot. Mutations found in lethal and localized prostate cancer patients are coded in
red and green, respectively. The y axis represents the total number of mutations identified.
AA = African Americans; BRCT = BRCA1 C-Terminal domain; CHN = Chinese; EA = European Americans; FAT = focal adhesion targeting; FATC = FRAP, ATM,
TRRAP C-terminal; PCa = prostate cancer.
Table 2 – Carrier rates of pathogenic/likely pathogenic mutations in
BRCA1/2
and
ATM
All
European American
African American
Chinese
Lethal
(
n
= 313)
Localized
(
n
= 486)
p
value Lethal
(
n
= 261)
Localized
(
n
= 352)
p
value Lethal
(
n
= 30)
Localized
(
n
= 89)
p
value Lethal
(
n
= 22)
Localized
(
n
= 45)
p
value
BRCA1
,
n
(%)
2 (0.64)
2 (0.41)
1.00
2 (0.77)
2 (0.57)
1.00 0 (0)
0 (0)
— 0 (0)
0 (0)
—
BRCA2
,
n
(%) 11 (3.51)
4 (0.82)
0.013
8 (3.07)
4 (1.12)
0.14 0 (0)
0 (0)
— 3 (13.64)
0 (0)
0.032
ATM
,
n
(%)
6 (1.92)
2 (0.41)
0.06
4 (1.53)
2 (0.57)
0.41 1 (3.33)
0 (0)
0.25 1 (4.55)
0 (0)
0.34
All,
n
(%)
19 (6.07)
7 (1.44
) a0.0007 14 (5.36)
7 (1.70
) a0.041 1 (3.33)
0 (0)
0.25 4 (18.18)
0 (0)
0.0095
a
One patient carries both
BRCA1
and
BRCA2
mutation.
E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 7 4 0 – 7 4 7
743