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Breast-ovarian cancer, familial, susceptibility to, 5(BROVCA5)

MedGen UID:
1841251
•Concept ID:
C5830615
•
Finding
Synonym: BROVCA5
 
Gene (location): PALB2 (16p12.2)
 
Monarch Initiative: MONDO:0957530
OMIM®: 620442

Definition

Individuals with mutation in the PALB2 gene have an increased risk of developing breast or, to a lesser degree, ovarian cancer. In addition, PALB2 variants increase susceptibility to several other cancers, e.g., male breast cancer and pancreatic cancer (PNCA3; 613348) (Rahman et al., 2007; Norquist et al., 2018; Yang et al., 2020). For a discussion of genetic heterogeneity of breast-ovarian cancer susceptibility, see BROVCA1 (604370). For general discussions of breast cancer and ovarian cancer, see 114480 and 167000, respectively. Reviews Hamdan and Nowak (2023) reviewed the structure and function of the PALB2 gene, and its role in disease, including Fanconi anemia (FANCN; 610832), pancreatic cancer (PNCA3; 613348), and breast and ovarian cancer. [from OMIM]

Clinical features

From HPO
Breast carcinoma
MedGen UID:
146260
•Concept ID:
C0678222
•
Neoplastic Process
The presence of a carcinoma of the breast.
See: Feature record | Search on this feature

Professional guidelines

PubMed

Retrospective Cohort Study on the Limitations of Direct-to-Consumer Genetic Screening in Hereditary Breast and Ovarian Cancer.
Desai NV, Barrows ED, Nielsen SM, Hatchell KE, Anderson MJ, Haverfield EV, Herrera B, Esplin ED, Lucassen A, Tung NM, Isaacs C
JCO Precis Oncol 2023 Aug;7:e2200695. doi: 10.1200/PO.22.00695. PMID: 37535880Free PMC Article
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.
US Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW Jr, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB
JAMA 2019 Aug 20;322(7):652-665. doi: 10.1001/jama.2019.10987. PMID: 31429903
Hereditary Cancer Syndromes-A Primer on Diagnosis and Management: Part 1: Breast-Ovarian Cancer Syndromes.
Samadder NJ, Giridhar KV, Baffy N, Riegert-Johnson D, Couch FJ
Mayo Clin Proc 2019 Jun;94(6):1084-1098. doi: 10.1016/j.mayocp.2019.02.017. PMID: 31171119

Recent clinical studies

Etiology

Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer.
Chen B, Zhang G, Li X, Ren C, Wang Y, Li K, Mok H, Cao L, Wen L, Jia M, Li C, Guo L, Wei G, Lin J, Li Y, Zhang Y, Han-Zhang H, Liu J, Lizaso A, Liao N
Aging (Albany NY) 2020 Feb 24;12(4):3140-3155. doi: 10.18632/aging.102783. PMID: 32091409Free PMC Article
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.
US Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW Jr, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB
JAMA 2019 Aug 20;322(7):652-665. doi: 10.1001/jama.2019.10987. PMID: 31429903
Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes.
Wang J, Li W, Shi Y, Huang Y, Sun T, Tang L, Lu Q, Lei Q, Liao N, Jin F, Li H, Huang T, Qian J, Pang D, Wang S, Fan P, Wu X, Lin Y, Qin H, Xu B
Cancer Med 2019 May;8(5):2074-2084. Epub 2019 Apr 13 doi: 10.1002/cam4.2093. PMID: 30982232Free PMC Article
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.
Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL
Am J Hum Genet 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024. PMID: 27153395Free PMC Article
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article

Diagnosis

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.
US Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW Jr, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB
JAMA 2019 Aug 20;322(7):652-665. doi: 10.1001/jama.2019.10987. PMID: 31429903
Hereditary Cancer Syndromes-A Primer on Diagnosis and Management: Part 1: Breast-Ovarian Cancer Syndromes.
Samadder NJ, Giridhar KV, Baffy N, Riegert-Johnson D, Couch FJ
Mayo Clin Proc 2019 Jun;94(6):1084-1098. doi: 10.1016/j.mayocp.2019.02.017. PMID: 31171119
Functional evaluation of variants of unknown significance in the BRCA2 gene identified in genetic testing.
Heczkova M, Machackova E, Macinga P, Gallmeier E, Cahova M, Spicak J, Jirsa M, Foretova L, Hucl T
Cancer Biol Ther 2019;20(5):633-641. Epub 2019 Jan 13 doi: 10.1080/15384047.2018.1550566. PMID: 30638113Free PMC Article
Current Approaches to Pancreatic Cancer Screening.
Chhoda A, Lu L, Clerkin BM, Risch H, Farrell JJ
Am J Pathol 2019 Jan;189(1):22-35. doi: 10.1016/j.ajpath.2018.09.013. PMID: 30558719
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article

Therapy

Uptake and Predictors of Opportunistic Salpingectomy for Ovarian Cancer Risk Reduction in the United States.
Karia PS, Joshu CE, Visvanathan K
Cancer Prev Res (Phila) 2021 Dec;14(12):1101-1110. Epub 2021 Aug 19 doi: 10.1158/1940-6207.CAPR-21-0121. PMID: 34413116Free PMC Article
Germline DNA Sequencing Reveals Novel Mutations Predictive of Overall Survival in a Cohort of Patients with Pancreatic Cancer.
Goldstein JB, Zhao L, Wang X, Ghelman Y, Overman MJ, Javle MM, Shroff RT, Varadhachary GR, Wolff RA, McAllister F, Futreal A, Fogelman DR
Clin Cancer Res 2020 Mar 15;26(6):1385-1394. Epub 2019 Dec 23 doi: 10.1158/1078-0432.CCR-19-0224. PMID: 31871297
Alcohol consumption, cigarette smoking, and familial breast cancer risk: findings from the Prospective Family Study Cohort (ProF-SC).
Zeinomar N, Knight JA, Genkinger JM, Phillips KA, Daly MB, Milne RL, Dite GS, Kehm RD, Liao Y, Southey MC, Chung WK, Giles GG, McLachlan SA, Friedlander ML, Weideman PC, Glendon G, Nesci S; kConFab Investigators, Andrulis IL, Buys SS, John EM, MacInnis RJ, Hopper JL, Terry MB
Breast Cancer Res 2019 Nov 28;21(1):128. doi: 10.1186/s13058-019-1213-1. PMID: 31779655Free PMC Article
BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer.
Jamard E, Volard B, Dugué AE, Legros A, Leconte A, Clarisse B, Davy G, Polycarpe F, Dugast C, Abadie C, Frebourg T, Tinat J, Tennevet I, Layet V, Joly F, Castéra L, Berthet P, Vaur D, Krieger S
Fam Cancer 2017 Apr;16(2):167-171. doi: 10.1007/s10689-016-9940-2. PMID: 27783335
The impact of risk information exposure on women's beliefs about direct-to-consumer genetic testing for BRCA mutations.
Gray SW, Hornik RC, Schwartz JS, Armstrong K
Clin Genet 2012 Jan;81(1):29-37. Epub 2011 Nov 2 doi: 10.1111/j.1399-0004.2011.01797.x. PMID: 21992449Free PMC Article

Prognosis

Germline DNA Sequencing Reveals Novel Mutations Predictive of Overall Survival in a Cohort of Patients with Pancreatic Cancer.
Goldstein JB, Zhao L, Wang X, Ghelman Y, Overman MJ, Javle MM, Shroff RT, Varadhachary GR, Wolff RA, McAllister F, Futreal A, Fogelman DR
Clin Cancer Res 2020 Mar 15;26(6):1385-1394. Epub 2019 Dec 23 doi: 10.1158/1078-0432.CCR-19-0224. PMID: 31871297
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article
International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.
Peixoto A, Santos C, Pinheiro M, Pinto P, Soares MJ, Rocha P, Gusmão L, Amorim A, van der Hout A, Gerdes AM, Thomassen M, Kruse TA, Cruger D, Sunde L, Bignon YJ, Uhrhammer N, Cornil L, Rouleau E, Lidereau R, Yannoukakos D, Pertesi M, Narod S, Royer R, Costa MM, Lazaro C, Feliubadaló L, Graña B, Blanco I, de la Hoya M, Caldés T, Maillet P, Benais-Pont G, Pardo B, Laitman Y, Friedman E, Velasco EA, Durán M, Miramar MD, Valle AR, Calvo MT, Vega A, Blanco A, Diez O, Gutiérrez-Enríquez S, Balmaña J, Ramon y Cajal T, Alonso C, Baiget M, Foulkes W, Tischkowitz M, Kyle R, Sabbaghian N, Ashton-Prolla P, Ewald IP, Rajkumar T, Mota-Vieira L, Giannini G, Gulino A, Achatz MI, Carraro DM, de Paillerets BB, Remenieras A, Benson C, Casadei S, King MC, Teugels E, Teixeira MR
Breast Cancer Res Treat 2011 Jun;127(3):671-9. Epub 2010 Jul 22 doi: 10.1007/s10549-010-1036-3. PMID: 20652400
A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients.
Sanz DJ, Acedo A, Infante M, Durán M, Pérez-Cabornero L, Esteban-Cardeñosa E, Lastra E, Pagani F, Miner C, Velasco EA
Clin Cancer Res 2010 Mar 15;16(6):1957-67. Epub 2010 Mar 9 doi: 10.1158/1078-0432.CCR-09-2564. PMID: 20215541
Familial pancreatic carcinoma in Jews.
Lynch HT, Deters CA, Lynch JF, Brand RE
Fam Cancer 2004;3(3-4):233-40. doi: 10.1007/s10689-004-9549-8. PMID: 15516847

Clinical prediction guides

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article
Unpacking the blockers: understanding perceptions and social constraints of health communication in hereditary breast ovarian cancer (HBOC) susceptibility families.
Peters JA, Kenen R, Hoskins LM, Koehly LM, Graubard B, Loud JT, Greene MH
J Genet Couns 2011 Oct;20(5):450-64. Epub 2011 May 6 doi: 10.1007/s10897-011-9370-0. PMID: 21547418Free PMC Article
International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.
Peixoto A, Santos C, Pinheiro M, Pinto P, Soares MJ, Rocha P, Gusmão L, Amorim A, van der Hout A, Gerdes AM, Thomassen M, Kruse TA, Cruger D, Sunde L, Bignon YJ, Uhrhammer N, Cornil L, Rouleau E, Lidereau R, Yannoukakos D, Pertesi M, Narod S, Royer R, Costa MM, Lazaro C, Feliubadaló L, Graña B, Blanco I, de la Hoya M, Caldés T, Maillet P, Benais-Pont G, Pardo B, Laitman Y, Friedman E, Velasco EA, Durán M, Miramar MD, Valle AR, Calvo MT, Vega A, Blanco A, Diez O, Gutiérrez-Enríquez S, Balmaña J, Ramon y Cajal T, Alonso C, Baiget M, Foulkes W, Tischkowitz M, Kyle R, Sabbaghian N, Ashton-Prolla P, Ewald IP, Rajkumar T, Mota-Vieira L, Giannini G, Gulino A, Achatz MI, Carraro DM, de Paillerets BB, Remenieras A, Benson C, Casadei S, King MC, Teugels E, Teixeira MR
Breast Cancer Res Treat 2011 Jun;127(3):671-9. Epub 2010 Jul 22 doi: 10.1007/s10549-010-1036-3. PMID: 20652400
A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients.
Sanz DJ, Acedo A, Infante M, Durán M, Pérez-Cabornero L, Esteban-Cardeñosa E, Lastra E, Pagani F, Miner C, Velasco EA
Clin Cancer Res 2010 Mar 15;16(6):1957-67. Epub 2010 Mar 9 doi: 10.1158/1078-0432.CCR-09-2564. PMID: 20215541
BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer.
Thomassen M, Hansen TV, Borg A, Lianee HT, Wikman F, Pedersen IS, Bisgaard ML, Nielsen FC, Kruse TA, Gerdes AM
Acta Oncol 2008;47(4):772-7. doi: 10.1080/02841860802004974. PMID: 18465347

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