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- Inherited NBN Mutations and Prostate Cancer Risk and Survival
- Bogna Rusak, Wojciech Kluźniak, Dominika Wokołorczykv, Klaudia Stempa, Aniruddh Kashyap, Jacek Gronwald, Tomasz Huzarski, Tadeusz Dębniak, Anna Jakubowska, Bartłomiej Masojć, Mohammad R. Akbari, Steven A. Narodv, Jan Lubiński, Cezary Cybulski, The Polish Hereditary Prostate Cancer Consortium
- Cancer Res Treat. 2019;51(3):1180-1187. Published online December 13, 2018
- DOI: https://doi.org/10.4143/crt.2018.532
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Abstract
PDF
Supplementary Material
PubReader
ePub - Purpose
To establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival.
Materials and Methods
Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q).
Results
The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004).
Conclusion
The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q). -
Citations
Citations to this article as recorded by
- Role of multi‑omics in advancing the understanding and treatment of prostate cancer (Review)
Li Yan, Pengxiao Su, Xiaoke Sun
Molecular Medicine Reports.2025; 31(5): 1. CrossRef - Identification of Genes with Rare Loss of Function Variants Associated with Aggressive Prostate Cancer and Survival
Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Sarah Wakerell, Koveela Govindasami, Reshma Rageevakumar, Nafisa Hussain, Andrea Osborne, Diana Keating, Artitaya Lophatananon, Kenneth R. Muir, Burcu F. Darst, David V. Conti, Christopher A. Haiman, Anton
European Urology Oncology.2024; 7(2): 248. CrossRef - Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta‐analysis
Barbora Stastna, Tatana Dolezalova, Katerina Matejkova, Barbora Nemcova, Petra Zemankova, Marketa Janatova, Petra Kleiblova, Jana Soukupova, Zdenek Kleibl
International Journal of Cancer.2024; 155(9): 1604. CrossRef - Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer
Burcu F. Darst, Ed Saunders, Tokhir Dadaev, Xin Sheng, Peggy Wan, Loreall Pooler, Lucy Y. Xia, Stephen Chanock, Sonja I. Berndt, Ying Wang, Alpa V. Patel, Demetrius Albanes, Stephanie J. Weinstein, Vincent Gnanapragasam, Chad Huff, Fergus J. Couch, Alicja
JAMA Oncology.2023; 9(11): 1514. CrossRef - Genetic aberrations of homologous recombination repair pathways in prostate cancer: The prognostic and therapeutic implications
Hamidreza Saeidi, Ikmal Hisyam Bakrin, Chandramathi Samudi Raju, Patimah Ismail, Mohsen Saraf, Mohd Ghani Khairul-Asri
Advances in Medical Sciences.2023; 68(2): 359. CrossRef - Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity
Gulnur Zhunussova, Nazgul Omarbayeva, Dilyara Kaidarova, Saltanat Abdikerim, Natalya Mit, Ilya Kisselev, Kanagat Yergali, Aigul Zhunussova, Tatyana Goncharova, Aliya Abdrakhmanova, Leyla Djansugurova
Oncotarget.2023; 14(1): 860. CrossRef - Genetic predisposition to prostate cancer: an update
Holly Ni Raghallaigh, Rosalind Eeles
Familial Cancer.2022; 21(1): 101. CrossRef - Association of germline rare pathogenic mutations in guideline‐recommended genes with prostate cancer progression: A meta‐analysis
Zhuqing Shi, Lucy Lu, William Kyle Resurreccion, Wancai Yang, Jun Wei, Qiang Wang, Valentina Engelmann, Siqun Lilly Zheng, Kathleen A. Cooney, William B. Isaacs, Brian T. Helfand, Jim Lu, Jianfeng Xu
The Prostate.2022; 82(1): 107. CrossRef - Clinical Significance of Gene Mutations and Polymorphic Variants and their Association with Prostate Cancer Risk in Polish Men
Marta Heise, Piotr Jarzemski, Dagmara Nowak, Aneta Bąk, Anna Junkiert-Czarnecka, Maria Pilarska-Deltow, Maciej Borysiak, Beata Pilarska, Olga Haus
Cancer Control.2022;[Epub] CrossRef - Prognostic Role of DNA Damage Response Genes Mutations and their Association With the Sensitivity of Olaparib in Prostate Cancer Patients
Dong Zhang, Xinchi Xu, Yuang Wei, Xinglin Chen, Guangyao Li, Zhongwen Lu, Xu Zhang, Xiaohan Ren, Shangqian Wang, Chao Qin
Cancer Control.2022;[Epub] CrossRef - Large Cancer Pedigree Involving Multiple Cancer Genes including Likely Digenic MSH2 and MSH6 Lynch Syndrome (LS) and an Instance of Recombinational Rescue from LS
Ingrid P. Vogelaar, Stephanie Greer, Fan Wang, GiWon Shin, Billy Lau, Yajing Hu, Sigurdis Haraldsdottir, Rocio Alvarez, Dennis Hazelett, Peter Nguyen, Francesca P. Aguirre, Maha Guindi, Andrew Hendifar, Jessica Balcom, Anna Leininger, Beth Fairbank, Hanle
Cancers.2022; 15(1): 228. CrossRef - Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study
Questa Karlsson, Mark N. Brook, Tokhir Dadaev, Sarah Wakerell, Edward J. Saunders, Kenneth Muir, David E. Neal, Graham G. Giles, Robert J. MacInnis, Stephen N. Thibodeau, Shannon K. McDonnell, Lisa Cannon-Albright, Manuel R. Teixeira, Paula Paulo, Marta C
European Urology Oncology.2021; 4(4): 570. CrossRef - Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes
Tiffany Davia Ricketts, Nestor Prieto-Dominguez, Pramod Sreerama Gowda, Eric Ubil
Frontiers in Immunology.2021;[Epub] CrossRef - Clinical Multigene Testing for Prostate Cancer
Tala Berro, Elizabeth Barrett, Saud H. AlDubayan
Urologic Clinics of North America.2021; 48(3): 297. CrossRef - Prostate Cancer Biomarkers: From diagnosis to prognosis and precision-guided therapeutics
Maria Adamaki, Vassilios Zoumpourlis
Pharmacology & Therapeutics.2021; 228: 107932. CrossRef - Observed evidence for guideline‐recommended genes in predicting prostate cancer risk from a large population‐based cohort
Jun Wei, Wancai Yang, Zhuqing Shi, Lucy Lu, Qiang Wang, W. Kyle Resurreccion, Valentina Engelmann, S. Lilly Zheng, Peter J. Hulick, Kathleen A. Cooney, William B. Isaacs, Brian T. Helfand, Jim Lu, Jianfeng Xu
The Prostate.2021; 81(13): 1002. CrossRef - NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
Keita Tomioka, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Hiromi Yanagihara, Kazumasa Fujita, Ekaterina Royba, Hiroshi Tauchi, Takashi Yamamoto, Iemasa Koh, Eiji Hirata, Yoshiki Kudo, Masao Kobayashi, Satoshi Okada, Shinya Matsuura
Scientific Reports.2021;[Epub] CrossRef - Applications of Deep Learning and Fuzzy Systems to Detect Cancer Mortality in Next-Generation Genomic Data
Cheng-Hong Yang, Sin-Hua Moi, Ming-Feng Hou, Li-Yeh Chuang, Yu-Da Lin
IEEE Transactions on Fuzzy Systems.2021; 29(12): 3833. CrossRef - Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019
Veda N. Giri, Karen E. Knudsen, William K. Kelly, Heather H. Cheng, Kathleen A. Cooney, Michael S. Cookson, William Dahut, Scott Weissman, Howard R. Soule, Daniel P. Petrylak, Adam P. Dicker, Saud H. AlDubayan, Amanda E. Toland, Colin C. Pritchard, Curtis
Journal of Clinical Oncology.2020; 38(24): 2798. CrossRef - Mutations in ATM, NBN and BRCA2 predispose to aggressive prostate cancer in Poland
Dominika Wokołorczyk, Wojciech Kluźniak, Tomasz Huzarski, Jacek Gronwald, Agata Szymiczek, Bogna Rusak, Klaudia Stempa, Katarzyna Gliniewicz, Aniruddh Kashyap, Sylwia Morawska, Tadeusz Dębniak, Anna Jakubowska, Marek Szwiec, Paweł Domagała, Jan Lubiński,
International Journal of Cancer.2020; 147(10): 2793. CrossRef - DNA Repair Syndromes and Cancer: Insights Into Genetics and Phenotype Patterns
Richa Sharma, Sara Lewis, Marcin W. Wlodarski
Frontiers in Pediatrics.2020;[Epub] CrossRef - Allelic modification of breast cancer risk in women with an NBN mutation
Bogna Rusak, Wojciech Kluźniak, Dominika Wokołorczyk, Klaudia Stempa, Aniruddh Kashyap, Helena Rudnicka, Jacek Gronwald, Tomasz Huzarski, Tadeusz Dębniak, Anna Jakubowska, Marek Szwiec, Mohammad R. Akbari, Steven A. Narod, Jan Lubiński, Cezary Cybulski
Breast Cancer Research and Treatment.2019; 178(2): 427. CrossRef
- Role of multi‑omics in advancing the understanding and treatment of prostate cancer (Review)
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- 301 Download
- 21 Web of Science
- 22 Crossref
- The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome
- Marcin R. Lener, Aniruddh Kashyap, Wojciech Kluźniak, Cezary Cybulski, Agnieszka Soluch, Sandra Pietrzak, Tomasz Huzarski, Jacek Gronwald, Jan Lubiński
- Cancer Res Treat. 2017;49(2):430-436. Published online July 28, 2016
- DOI: https://doi.org/10.4143/crt.2016.217
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible associationwith the familial pancreatic cancer (FPC) risk in Poland.
Materials and Methods
In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations in BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes.
Results
A statistically significant association was observed between the 172_175delTTGT mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer and CHEK2 mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T of CHEK2 (OR, 2.17; p=0.026).
Conclusion
The founder mutations in the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome. -
Citations
Citations to this article as recorded by- Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target
Yucheng An, Duolun Gao, Yanjie He, Nan Ge, Jintao Guo, Siyu Sun, Caixia Wang, Fan Yang
Genes & Diseases.2025; 12(1): 101191. CrossRef - CHEK2 germline variants identified in familial nonmedullary thyroid cancer lead to impaired protein structure and function
Carolina Pires, Inês J. Marques, Mariana Valério, Ana Saramago, Paulo E. Santo, Sandra Santos, Margarida Silva, Margarida M. Moura, João Matos, Teresa Pereira, Rafael Cabrera, Diana Lousa, Valeriano Leite, Tiago M. Bandeiras, João B. Vicente, Branca M. Ca
Journal of Biological Chemistry.2024; 300(3): 105767. CrossRef - The role of germline BRCA1 & BRCA2 mutations in familial pancreatic cancer: A systematic review and meta-analysis
Edward Kurnia Setiawan Limijadi, Muflihatul Muniroh, Yan Wisnu Prajoko, Kevin Christian Tjandra, Danendra Rakha Putra Respati, Alvaro Galli
PLOS ONE.2024; 19(5): e0299276. CrossRef - Germline variant profiling of CHEK2 sequencing variants in breast cancer patients
Claire McCarthy-Leo, Scott Baughan, Hunter Dlugas, Prisca Abraham, Janice Gibbons, Carolyn Baldwin, Sarah Chung, Gerald L. Feldman, Gregory Dyson, Russell L. Finley, Michael A. Tainsky
Cancer Genetics.2024; 288-289: 10. CrossRef - Management of individuals with germline pathogenic/likely pathogenic variants in CHEK2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
Helen Hanson, Esteban Astiazaran-Symonds, Laura M. Amendola, Judith Balmaña, William D. Foulkes, Paul James, Susan Klugman, Joanne Ngeow, Rita Schmutzler, Nicoleta Voian, Myra J. Wick, Tuya Pal, Marc Tischkowitz, Douglas R. Stewart
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BMC Cancer.2021;[Epub] CrossRef - Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients
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Cancers.2021; 13(17): 4430. CrossRef - Assembling and Validating Bioinformatic Pipelines for Next-Generation Sequencing Clinical Assays
Jeffrey A SoRelle, Megan Wachsmann, Brandi L. Cantarel
Archives of Pathology & Laboratory Medicine.2020; 144(9): 1118. CrossRef - Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer
Matthew B. Yurgelun, Anu B. Chittenden, Vicente Morales-Oyarvide, Douglas A. Rubinson, Richard F. Dunne, Margaret M. Kozak, Zhi Rong Qian, Marisa W. Welch, Lauren K. Brais, Annacarolina Da Silva, Justin L. Bui, Chen Yuan, Tingting Li, Wanwan Li, Atsuhiro
Genetics in Medicine.2019; 21(1): 213. CrossRef - Genomic Features and Clinical Management of Patients with Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer
Akihiro Ohmoto, Shinichi Yachida, Chigusa Morizane
International Journal of Molecular Sciences.2019; 20(3): 561. CrossRef - Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma
O. Obazee, L. Archibugi, A. Andriulli, P. Soucek, E. Małecka‐Panas, A. Ivanauskas, T. Johnson, M. Gazouli, T. Pausch, R. T. Lawlor, G. M. Cavestro, A. C. Milanetto, M. Di Leo, C. Pasquali, P. Hegyi, A. Szentesi, C. E. Radu, C. Gheorghe, G. E. Theodoropoul
International Journal of Cancer.2019; 145(3): 686. CrossRef - Progress report: familial pancreatic cancer
Ioannis Mintziras, Detlef K. Bartsch
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G.A. Yanus, T.A. Akhapkina, A.O. Ivantsov, E.V. Preobrazhenskaya, S.N. Aleksakhina, I.V. Bizin, A.P. Sokolenko, N.V. Mitiushkina, E.Sh. Kuligina, E.N. Suspitsin, A.R. Venina, M.M. Holmatov, O.A. Zaitseva, O.S. Yatsuk, D.V. Pashkov, A.M. Belyaev, A.V. Togo
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Journal of Gastroenterology.2018; 53(10): 1159. CrossRef - Germline Variants and Risk for Pancreatic Cancer
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