1Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
2Department of Clinical Genetics and Pathology, University of Zielona Góra, Zielona Góra, Poland
3Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland
4West Pomeranian Oncology Center, Szczecin, Poland
5Women’s College Research Institute, University of Toronto, Toronto, Canada
Copyright © 2019 by the Korean Cancer Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
* The Polish Hereditary Prostate Cancer Consortium
Other members of the Polish Hereditary Prostate Cancer Consortium: Adam Gołąb1, Bartłomiej Gliniewicz2, Andrzej Sikorski1, Marcin Słojewski1, Jerzy Świtała2, Tomasz Borkowski3, Andrzej Borkowski3, Andrzej Antczak4, Łukasz Wojnar4, Jacek Przybyła5, Marek Sosnowski5, Bartosz Małkiewicz6, Romuald Zdrojowy6, Paulina Sikorska-Radek7, Jozef Matych7, Jacek Wilkosz8, Waldemar Rożański8, Jacek Kiś9, Krzysztof Bar9, Piotr Bryniarski10, Andrzej Paradysz10, Konrad Jersak11, Jerzy Niemirowicz11, Piotr Słupski12, Piotr Jarzemski12, Michał Skrzypczyk13, Jakub Dobruch13, Paweł Domagała14, Bohdan Gorski15, Tomasz Byrski16, Michał Puszyński2, Michał Soczawa1, Sławomir Archimowicz2, Mirosław Kordowski2, Marcin Życzkowski10, Andrzej Borowka13, Joanna Bagińska17, Kazimierz Krajka17, Marek Szwiec18, Małgorzata Stawicka19, Olga Haus20, Hanna Janiszewska20, Agnieszka Stembalska21, Maria Małgorzata Sąsiadek21
1Clinic of Urology, Pomeranian Medical University, Szczecin, 2Division of Urology, Maria Skłodowska-Curie Hospital, Szczecin, 3Department of Urology, Medical University, Warszawa, 4Chair of Urology, Medical University, Poznan, 5Department of Urology, Medical University of Lodz, Łodź, 6Department of Urology and Urological Oncology, University of Medicine, Wrocław, 7Division of Urology, Regional Hospital, Łódź, 8Second Department of Urology, Medical University of Lodz, Łodź, 9Department of Urology, University Hospital of Lublin, Lublin, 10Department of Urology, Medical University of Silesia, Zabrze, 11Department of Urology, Ministry of Internal Affairs and Administration Hospital, Łódź, 12Department of Urology, J. Biziel Hospital, Bydgoszcz, 13Department of Urology, Centre of Postgraduate Urology Education, Warsaw, 14Department of Pathology, Pomeranian Medical University, Szczecin, 15Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, 16Department of Oncology, Pomeranian Medical University, Szczecin, 17Clinic of Urology, Medical University, Gdansk, 18Department of Clinical Oncology, University Hospital in Zielona Gora, 19Department of Clinical Genetics and Pathology, University of Zielona Góra, Zielona Góra, 20Department of Clinical Genetics, Nicolaus Copernicus University, Bydgoszcz, 21Department of Genetics, Wroclaw Medical University, Wrocław, Poland
NBN variant |
Unselected prostate cancer cases |
Familial prostate cancer cases |
Control No./Total (%) | ||||
---|---|---|---|---|---|---|---|
No./Total (%) | OR (95% CI) | p-value | No./Total (%) | OR (95% CI) | p-value | ||
657del5 | 74/5,189 (1.4) | 2.5 (1.7-3.8) | < 0.001 | 15/635 (2.4) | 4.2 (2.3-7.8) | < 0.001 | 35/6,152 (0.6) |
R215W | 13/5,189 (0.25) | 1.3 (0.5-3.4) | 0.762 | 2/635 (0.3) | 1.6 (0.3-8.2) | 0.889 | 6/3,122a) (0.2) |
I171V | 140/5,189 (2.7) | 1.2 (0.9-1.5) | 0.351 | 8/635 (1.3) | 0.5 (0.3-1.1) | 0.120 | 73/3,122a) (2.3) |
E185Q (GG genotype) | 2,207/5,189 (42.6) | 1.0 (0.9-1.1) | 0.994 | 270/634 (42.6) | 1.0 (0.8-1.2) | 0.982 | 2,617/6,152 (42.5) |
E185Q (GC genotype) | 2,389/5,189 (46.0) | 1.0 (0.9-1.1) | 0.565 | 287/634 (45.3) | 1.0 (0.8-1.2) | 0.952 | 2,798/6,152 (45.5) |
E185Q (CC genotype) | 593/5,189 (11.4) | 0.9 (0.8-1.1) | 0.379 | 77/518 (12.1) | 1.0 (0.8-1.3) | 0.954 | 737/6,152 (12.0) |
657del5 mutation (n=74) | p-value | 657del5 and E185Q GG genotype (n=50) | p-value | 657del5 and E185Q non-GG genotype (n=24) | p-value | Neither genotypea) (n=2,958) | |
---|---|---|---|---|---|---|---|
Age of diagnosis (yr) | |||||||
Mean | 67.0 | 0.505 | 67.0 | 0.586 | 67.0 | 0.697 | 67.8 |
PSA level at diagnosis (ng/mL) | |||||||
Median | 11.7 | 0.592 | 13.4 | 0.237 | 8.6 | 0.532 | 11.8 |
≤ 4.0 | 1/44 (2.3) | 0.724 | 1/27 (3.7) | 1.000 | 0/17 (0.0) | 1.000 | 86/1,652 (5.2) |
4.1-10 | 17/44 (38.6) | 1.000 | 6/27 (22.2) | 0.077 | 11/17 (64.7) | 0.044 | 647/1,652 (39.2) |
10.1-20.0 | 11/44 (25.0) | 1.000 | 9/27 (33.3) | 0.367 | 2/17 (11.8) | 0.271 | 407/1,652 (24.6) |
> 20.0 | 15/44 (34.1) | 0.742 | 11/27 (40.7) | 0.297 | 4/17 (23.5) | 0.607 | 512/1,652 (30.1) |
Gleason score | |||||||
< 7 | 25/54 (47.2) | 0.522 | 17/36 (47.2) | 0.618 | 8/18 (44.4) | 0.638 | 1,011/1,957 (51.7) |
7 | 15/54 (28.3) | 0.892 | 8/36 (22.2) | 0.460 | 7/18 (38.9) | 0.438 | 579/1,957 (29.6) |
> 7 | 14/54 (24.5) | 0.250 | 11/36 (30.6) | 0.085 | 3/18 (16.7) | 1.000 | 367/1,957 (18.7) |
Stage | |||||||
T1 | 14/49 (28.6) | 0.755 | 7/32 (21.9) | 0.256 | 7/17 (41.2) | 0.437 | 467/1,467 (31.8) |
T2 | 16/49 (32.7) | 0.186 | 11/32 (34.4) | 0.370 | 5/17 (29.4) | 0.328 | 632/1,467 (43.1) |
T3 | 8/49 (16.3) | 0.852 | 5/32 (15.6) | 0.820 | 3/17 (17.6) | 1.000 | 272/1,467 (18.5) |
T4 | 11/49 (22.4) | 0.0004 | 9/32 (28.1) | 0.0002 | 2/17 (11.8) | 0.311 | 96/1,467 (6.5) |
T3 or T4 | 19/49 (38.8) | 0.044 | 14/32 (43.7) | 0.023 | 5/17 (29.4) | 0.778 | 368/1,467 (25.1) |
Men with 657del5 mutation (n=74) | Men with 657del5 and E185Q GG genotype (n=50) | Men with 657del5 and E185Q non-GG genotype (n=24) | Men with neither genotypea) (n=2,956) | |
---|---|---|---|---|
Median follow-up (mo) | 90 | 90 | 87 | 106 |
Proportion of deceased (%) | 56.8 | 62.0 | 45.8 | 43.8 |
Median survival (mo) | 81 | 78 | 95 | 132 |
5-Year survival (%) | 56 | 51 | 66 | 69 |
10-Year survival (%) | 34 | 28 | 45 | 53 |
HR | 1.6 | 2.0 | 1.1 | 1.0a) |
95% CI | 1.1-2.5 | 1.2-3.2 | 0.6-2.2 | - |
p-value | 0.001 | 0.0001 | 0.659 | - |
NBN variant | Unselected prostate cancer cases |
Familial prostate cancer cases |
Control No./Total (%) | ||||
---|---|---|---|---|---|---|---|
No./Total (%) | OR (95% CI) | p-value | No./Total (%) | OR (95% CI) | p-value | ||
657del5 | 74/5,189 (1.4) | 2.5 (1.7-3.8) | < 0.001 | 15/635 (2.4) | 4.2 (2.3-7.8) | < 0.001 | 35/6,152 (0.6) |
R215W | 13/5,189 (0.25) | 1.3 (0.5-3.4) | 0.762 | 2/635 (0.3) | 1.6 (0.3-8.2) | 0.889 | 6/3,122 |
I171V | 140/5,189 (2.7) | 1.2 (0.9-1.5) | 0.351 | 8/635 (1.3) | 0.5 (0.3-1.1) | 0.120 | 73/3,122 |
E185Q (GG genotype) | 2,207/5,189 (42.6) | 1.0 (0.9-1.1) | 0.994 | 270/634 (42.6) | 1.0 (0.8-1.2) | 0.982 | 2,617/6,152 (42.5) |
E185Q (GC genotype) | 2,389/5,189 (46.0) | 1.0 (0.9-1.1) | 0.565 | 287/634 (45.3) | 1.0 (0.8-1.2) | 0.952 | 2,798/6,152 (45.5) |
E185Q (CC genotype) | 593/5,189 (11.4) | 0.9 (0.8-1.1) | 0.379 | 77/518 (12.1) | 1.0 (0.8-1.3) | 0.954 | 737/6,152 (12.0) |
Variants present | Unselected prostate cancer cases |
Familial prostate cancer cases |
Control No. | ||||
---|---|---|---|---|---|---|---|
No. | OR (95% Cl) | p-value | No. | OR (95% Cl) | p-value | ||
Effect of NBN 657del5 on cancer risk among carriers of GG genotype of E185Q | |||||||
NBN 657del5–negative and GG genotype | 2,157 | 4.4 (2.4-8.0) | < 0.001 | 260 | 7.2 (3.1-16.3) | < 0.001 | 2,603 |
NBN 657del5–positive and GG genotype | 50 | 10 | 14 | 14 | |||
Effect of NBN 657del5 on cancer risk among carriers of GC/CC genotype of E185Q | |||||||
NBN 657del5–negative and GC/CC genotype | 2,958 | 1.4 (0.8-2.4) | 0.382 | 359 | 2.3 (0.9-6.2) | 0.161 | 3,514 |
NBN 657del5–positive and GC/CC genotype | 24 | 5 | 21 |
657del5 mutation (n=74) | p-value | 657del5 and E185Q GG genotype (n=50) | p-value | 657del5 and E185Q non-GG genotype (n=24) | p-value | Neither genotype |
|
---|---|---|---|---|---|---|---|
Age of diagnosis (yr) | |||||||
Mean | 67.0 | 0.505 | 67.0 | 0.586 | 67.0 | 0.697 | 67.8 |
PSA level at diagnosis (ng/mL) | |||||||
Median | 11.7 | 0.592 | 13.4 | 0.237 | 8.6 | 0.532 | 11.8 |
≤ 4.0 | 1/44 (2.3) | 0.724 | 1/27 (3.7) | 1.000 | 0/17 (0.0) | 1.000 | 86/1,652 (5.2) |
4.1-10 | 17/44 (38.6) | 1.000 | 6/27 (22.2) | 0.077 | 11/17 (64.7) | 0.044 | 647/1,652 (39.2) |
10.1-20.0 | 11/44 (25.0) | 1.000 | 9/27 (33.3) | 0.367 | 2/17 (11.8) | 0.271 | 407/1,652 (24.6) |
> 20.0 | 15/44 (34.1) | 0.742 | 11/27 (40.7) | 0.297 | 4/17 (23.5) | 0.607 | 512/1,652 (30.1) |
Gleason score | |||||||
< 7 | 25/54 (47.2) | 0.522 | 17/36 (47.2) | 0.618 | 8/18 (44.4) | 0.638 | 1,011/1,957 (51.7) |
7 | 15/54 (28.3) | 0.892 | 8/36 (22.2) | 0.460 | 7/18 (38.9) | 0.438 | 579/1,957 (29.6) |
> 7 | 14/54 (24.5) | 0.250 | 11/36 (30.6) | 0.085 | 3/18 (16.7) | 1.000 | 367/1,957 (18.7) |
Stage | |||||||
T1 | 14/49 (28.6) | 0.755 | 7/32 (21.9) | 0.256 | 7/17 (41.2) | 0.437 | 467/1,467 (31.8) |
T2 | 16/49 (32.7) | 0.186 | 11/32 (34.4) | 0.370 | 5/17 (29.4) | 0.328 | 632/1,467 (43.1) |
T3 | 8/49 (16.3) | 0.852 | 5/32 (15.6) | 0.820 | 3/17 (17.6) | 1.000 | 272/1,467 (18.5) |
T4 | 11/49 (22.4) | 0.0004 | 9/32 (28.1) | 0.0002 | 2/17 (11.8) | 0.311 | 96/1,467 (6.5) |
T3 or T4 | 19/49 (38.8) | 0.044 | 14/32 (43.7) | 0.023 | 5/17 (29.4) | 0.778 | 368/1,467 (25.1) |
Men with 657del5 mutation (n=74) | Men with 657del5 and E185Q GG genotype (n=50) | Men with 657del5 and E185Q non-GG genotype (n=24) | Men with neither genotype |
|
---|---|---|---|---|
Median follow-up (mo) | 90 | 90 | 87 | 106 |
Proportion of deceased (%) | 56.8 | 62.0 | 45.8 | 43.8 |
Median survival (mo) | 81 | 78 | 95 | 132 |
5-Year survival (%) | 56 | 51 | 66 | 69 |
10-Year survival (%) | 34 | 28 | 45 | 53 |
HR | 1.6 | 2.0 | 1.1 | 1.0 |
95% CI | 1.1-2.5 | 1.2-3.2 | 0.6-2.2 | - |
p-value | 0.001 | 0.0001 | 0.659 | - |
OR, odds ratio; CI, confidence interval. For
OR, odds ratio; CI, confidence interval.
Values are presented as number (%) unless otherwise indicated. p-values are calculated with respect to carriers of neither genotype (657del5 negative and E185Q GG genotype negative cases) as reference group.
Hazard ratio (HR), 95% confidence interval (CI), and p-values are calculated by log-rank test. Reference group (men with prostate cancer without 657del5 and without GG genotype of E185Q.