Details of Disease

General Information of Disease (ID: DISWDUGU)

• Disease Name: Hereditary breast ovarian cancer syndrome
• Synonyms: syndromes, HBOC; syndrome, HBOC; hereditary breast ovarian cancer; HBOC syndromes; HBOC syndrome; hereditary breast/ovarian cancer (BRCA1, BRCA2); hereditary breast ovarian cancer syndrome; hereditary breast and ovarian cancer syndrome; hereditary breast and ovarian cancer; familial breast/ovarian cancer (BRCA1, BRCA2); familial breast and ovarian cancer syndrome; Hereditary Breast and Ovarian Cancer Syndrome; BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC); BRCA1- and BRCA2-associated hereditary breast and ovarian cancer
• Definition: An autosomal dominant inherited syndrome caused by mutations in the BRCA1 or BRCA2 genes. Patients are at high risk of developing breast cancer, particularly before the age of fifty, high risk of developing a second primary breast cancer, and high risk of developing both breast and ovarian cancer.
• Disease Hierarchy:
  DIS3HIWD: Autosomal dominant disease
  DISGXLG5: Hereditary neoplastic syndrome
  DISWDUGU: Hereditary breast ovarian cancer syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0003582
  MESH ID: D061325
  UMLS CUI: C0677776
  MedGen ID: 151793
  Orphanet ID: 145
  SNOMED CT ID: 718220008

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CHEK2	TT9ABMF	Limited	Genetic Variation	[1]
BRCA2	TTUARD6	Supportive	Autosomal dominant	[2]
HSD17B1	TTIWB6L	moderate	Biomarker	[3]
HSD17B13	TTDJYZR	moderate	Genetic Variation	[3]
PRSS1	TT2WR1T	moderate	Genetic Variation	[4]
SLC22A12	TTA592U	moderate	Biomarker	[5]
BRIP1	TTZV7LJ	Strong	Genetic Variation	[6]
FANCA	TTV5HJS	Strong	Biomarker	[7]
HOXB13	TTZ6I58	Strong	Genetic Variation	[8]
MLH1	TTISG27	Strong	Genetic Variation	[9]
MSH2	TTCAWRT	Strong	Genetic Variation	[10]
PMS1	TTX1ISF	Strong	Genetic Variation	[11]
PTEN	TTXJ3W7	Strong	Genetic Variation	[12]
RAD51	TTC0G1L	Strong	Genetic Variation	[13]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HSD17B7	DEDMWFX	moderate	Genetic Variation	[3]

This Disease Is Related to 20 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SEM1	OTASLBM1	Limited	Genetic Variation	[14]
BRCA1	OT5BN6VH	Supportive	Autosomal dominant	[2]
BRCA2	OTF1XSV1	Supportive	Autosomal dominant	[2]
RAD51C	OTUD6SY5	Supportive	Autosomal dominant	[15]
RAD51D	OTKOU5XN	Supportive	Autosomal dominant	[16]
ALYREF	OTOF2ADD	moderate	Genetic Variation	[17]
C11orf65	OTKOIR0G	moderate	Genetic Variation	[18]
DHRS11	OTU3J0ZL	moderate	Genetic Variation	[3]
DHX8	OT97S0IH	moderate	Genetic Variation	[19]
EMSY	OTBQ3KQE	moderate	Altered Expression	[20]
OLA1	OTAPOTTG	moderate	Genetic Variation	[21]
RAD51B	OTCJVRMY	moderate	Genetic Variation	[18]
RASSF7	OT0V4EIZ	moderate	Genetic Variation	[22]
S100A2	OTTGHJ1H	moderate	Biomarker	[23]
BARD1	OTTC0Z9Y	Strong	CausalMutation	[24]
BCCIP	OTFFKG79	Strong	Genetic Variation	[25]
MRE11	OTGU8TZM	Strong	Genetic Variation	[18]
NBN	OT73B5MD	Strong	Genetic Variation	[26]
PMS2	OTNLWTMI	Strong	Genetic Variation	[27]
RAD50	OTYMU9G1	Strong	Genetic Variation	[28]

References

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• [2] Hereditary ovarian cancer. Hum Pathol. 2005 Aug;36(8):861-70. doi: 10.1016/j.humpath.2005.06.006.
• [3] Detection of polymorphisms in the estradiol 17 beta-hydroxysteroid dehydrogenase II gene at the EDH17B2 locus on 17q11-q21.Hum Mol Genet. 1993 Apr;2(4):479-83. doi: 10.1093/hmg/2.4.479.
• [4] Familial pancreatic cancer: genetic advances.Genes Dev. 2014 Jan 1;28(1):1-7. doi: 10.1101/gad.228452.113.
• [5] Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.Ann Surg Oncol. 2014 Oct;21(10):3342-7. doi: 10.1245/s10434-014-3921-1. Epub 2014 Jul 22.
• [6] The effects of genomic germline variant reclassification on clinical cancer care.Oncotarget. 2019 Jan 11;10(4):417-423. doi: 10.18632/oncotarget.26501. eCollection 2019 Jan 11.
• [7] Hereditary breast and ovarian cancer susceptibility genes (review).Oncol Rep. 2013 Sep;30(3):1019-29. doi: 10.3892/or.2013.2541. Epub 2013 Jun 19.
• [8] Familial prostate cancer.Semin Oncol. 2016 Oct;43(5):560-565. doi: 10.1053/j.seminoncol.2016.08.001. Epub 2016 Aug 18.
• [9] The importance of proper bioinformatics analysis and clinical interpretation of tumor genomic profiling: a case study of undifferentiated sarcoma and a constitutional pathogenic BRCA2 mutation and an MLH1 variant of uncertain significance.Fam Cancer. 2015 Sep;14(3):481-5. doi: 10.1007/s10689-015-9790-3.
• [10] The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer.Fam Cancer. 2016 Jan;15(1):111-21. doi: 10.1007/s10689-015-9832-x.
• [11] Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for breast and ovarian cancer.Eur J Cancer Prev. 2000 Jun;9(3):139-50.
• [12] PTEN germline mutations in patients initially tested for other hereditary cancer syndromes: would use of risk assessment tools reduce genetic testing?.Oncologist. 2013;18(10):1083-90. doi: 10.1634/theoncologist.2013-0174. Epub 2013 Sep 13.
• [13] RAD51 135G>C and TP53 Arg72Pro polymorphisms and susceptibility to breast cancer in Serbian women.Fam Cancer. 2014 Jun;13(2):173-80. doi: 10.1007/s10689-013-9690-3.
• [14] Mutation analysis of the SHFM1 gene in breast/ovarian cancer families.J Cancer Res Clin Oncol. 2013 Mar;139(3):529-32. doi: 10.1007/s00432-013-1385-5. Epub 2013 Feb 1.
• [15] Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet. 2010 May;42(5):410-4. doi: 10.1038/ng.569. Epub 2010 Apr 18.
• [16] Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet. 2011 Aug 7;43(9):879-882. doi: 10.1038/ng.893.
• [17] Enhanced detection of mutations in BRCA1 exon 11 using restriction endonuclease fingerprinting-single-strand conformation polymorphism.J Mol Med (Berl). 2000;78(10):580-7. doi: 10.1007/s001090000147.
• [18] Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.Hum Mutat. 2016 Jul;37(7):640-52. doi: 10.1002/humu.22972. Epub 2016 Mar 18.
• [19] A tandem duplication of BRCA1 exons 1-19 through DHX8 exon 2 in four families with hereditary breast and ovarian cancer syndrome.Breast Cancer Res Treat. 2018 Dec;172(3):561-569. doi: 10.1007/s10549-018-4957-x. Epub 2018 Sep 6.
• [20] EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases.Mol Genet Genomics. 2011 Apr;285(4):325-40. doi: 10.1007/s00438-011-0612-5. Epub 2011 Mar 16.
• [21] OLA1 gene sequencing in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer.Breast Cancer. 2017 Mar;24(2):336-340. doi: 10.1007/s12282-016-0709-0. Epub 2016 Jun 6.
• [22] Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus.Nat Genet. 1996 Mar;12(3):309-11. doi: 10.1038/ng0396-309.
• [23] S100A2 is a BRCA1/p63 coregulated tumour suppressor gene with roles in the regulation of mutant p53 stability.Cell Death Dis. 2014 Feb 20;5(2):e1070. doi: 10.1038/cddis.2014.31.
• [24] BARD1 nonsense variant c.1921C>T in a patient with recurrent breast cancer.Clin Case Rep. 2017 Jan 4;5(2):104-107. doi: 10.1002/ccr3.793. eCollection 2017 Feb.
• [25] Mutation analysis of the BCCIP gene for breast cancer susceptibility in breast/ovarian cancer families.Gynecol Oncol. 2013 Nov;131(2):460-3. doi: 10.1016/j.ygyno.2013.07.104. Epub 2013 Jul 31.
• [26] Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.Eur J Hum Genet. 2014 Nov;22(11):1305-13. doi: 10.1038/ejhg.2014.16. Epub 2014 Feb 19.
• [27] The rate of the recurrent MSH6 mutations in Ashkenazi Jewish breast cancer patients.Cancer Causes Control. 2019 Jan;30(1):97-101. doi: 10.1007/s10552-018-1106-0. Epub 2018 Nov 30.
• [28] Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18032-7. doi: 10.1073/pnas.1115052108. Epub 2011 Oct 17.