An inherited NBN mutation is associated with poor prognosis prostate cancer

被引：81

作者：

Cybulski, C. ^{[1
]}

Wokolorczyk, D. ^{[1
]}

Kluzniak, W. ^{[1
]}

Jakubowska, A. ^{[1
]}

Gorski, B. ^{[1
]}

Gronwald, J. ^{[1
]}

Huzarski, T. ^{[1
]}

Kashyap, A. ^{[1
]}

Byrski, T. ^{[1
]}

Debniak, T. ^{[1
]}

Golab, A. ^{[2
]}

Gliniewicz, B. ^{[2
,3
]}

Sikorski, A. ^{[2
]}

Switala, J. ^{[3
]}

Borkowski, T. ^{[4
]}

Borkowski, A. ^{[4
]}

Antczak, A. ^{[5
]}

Wojnar, L. ^{[5
]}

Przybya, J. ^{[6
]}

Sosnowski, M. ^{[6
]}

Malkiewicz, B. ^{[7
]}

Zdrojowy, R. ^{[7
]}

Sikorska-Radek, P. ^{[8
]}

Matych, J. ^{[8
]}

Wilkosz, J. ^{[9
]}

Rozanski, W. ^{[9
]}

Kis, J. ^{[10
]}

Bar, K. ^{[10
]}

Bryniarski, P. ^{[11
]}

Paradysz, A. ^{[11
]}

Jersak, K.

Niemirowicz, J. ^{[12
]}

Slupski, P. ^{[13
]}

Jarzemski, P. ^{[13
]}

Skrzypczyk, M. ^{[14
]}

Dobruch, J. ^{[14
]}

Domagala, P. ^{[15
]}

Narod, S. A.

Lubinski, J. ^{[16
]}

机构：

[1] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-70115 Szczecin, Poland

[2] Pomeranian Med Univ, Clin Urol, PL-70115 Szczecin, Poland

[3] Maria Sklodowska Curie Hosp, Div Urol, Szczecin, Poland

[4] Med Univ, Dept Urol, Warsaw, Poland

[5] Med Univ, Chair Urol, Poznan, Poland

[6] Med Univ Lodz, Dept Urol, Lodz, Poland

[7] Univ Med, Dept Urol & Urol Oncol, Wroclaw, Poland

[8] Reg Hosp, Div Urol, Lodz, Poland

[9] Med Univ Lodz, Dept Urol 2, Lodz, Poland

[10] Univ Hosp Lublin, Dept Urol, Lublin, Poland

[11] Med Univ Silesia, Dept Urol, Zabrze, Poland

[12] Minist Internal Affairs & Adm Hosp, Dept Urol, Lodz, Poland

[13] J Biziel Hosp, Dept Urol, Bydgoszcz, Poland

[14] Ctr Postgrad Urol Educ, Dept Urol, Warsaw, Poland

[15] Pomeranian Med Univ, Dept Pathol, PL-70115 Szczecin, Poland

[16] Ctr Res Womens Hlth, Toronto, ON, Canada

来源：

BRITISH JOURNAL OF CANCER | 2013年 / 108卷 / 02期

关键词：

BRCA1; NBS1; NBN; CHEK2; aggressive prostate cancer; survival; GERMLINE MUTATIONS; BREAST-CANCER; CARRIER FREQUENCY; BRCA2; MUTATIONS; INCREASED RISK; GENE; MEN; PROTEIN; FAMILIES; NBS1;

D O I：

10.1038/bjc.2012.486

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. Methods: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). Results: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age <= 60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. Conclusion: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.

引用

页码：461 / 468

页数：8

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