Skip to main content
SpringerLink
Log in

BRCA and Breast Cancer-Related High-Penetrance Genes

  • Chapter
  • First Online:
Translational Research in Breast Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1187))

Abstract

Genetic susceptibility explains 5–10% of all breast cancer cases. High-penetrance breast cancer susceptibility genes deliberate a greater than tenfold relative risk of breast cancer. BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer, and TP53, PTEN, and SKT11 (LKB1) are rarely present. The prevalence of BRCA1 and BRCA2 genetic alterations differ in various ethnic groups. The Korean Hereditary Breast Cancer (KOHBRA) Study, nationwide-scale study, was established to acquire evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea prospectively since 2007. In this chapter, we review previous research related to hereditary breast cancer and summarize the present concepts and research results centered on the Korean Hereditary Breast Cancer Research at this time.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77(11):2318–24.

    Article  CAS  PubMed  Google Scholar 

  2. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182):66–71.

    Article  CAS  PubMed  Google Scholar 

  3. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378(6559):789–92.

    Article  CAS  PubMed  Google Scholar 

  4. Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene. 2006;25(43):5864–74.

    Article  CAS  PubMed  Google Scholar 

  5. Antoniou AC, Easton DF. Models of genetic susceptibility to breast cancer. Oncogene. 2006;25(43):5898–905.

    Article  CAS  PubMed  Google Scholar 

  6. Smith P, McGuffog L, Easton DF, Mann GJ, Pupo GM, Newman B, et al. A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer. 2006;45(7):646–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Foulkes WD. Inherited susceptibility to common cancers. N Engl J Med. 2008;359(20):2143–53.

    Article  CAS  PubMed  Google Scholar 

  8. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lalloo F, Varley J, Moran A, Ellis D, O'Dair L, Pharoah P, et al. BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives. Eur J Cancer. 2006;42(8):1143–50.

    Article  CAS  PubMed  Google Scholar 

  10. Hobert JA, Eng C. PTEN hamartoma tumor syndrome: an overview. Genet Med. 2009;11(10):687.

    Article  CAS  PubMed  Google Scholar 

  11. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Human Genet. 1998;62(3):676–89.

    Article  CAS  Google Scholar 

  12. C-BC C. Low-penetrance susceptibility to breast cancer due to CHEK2* 1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31(1):55.

    Article  CAS  Google Scholar 

  13. Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371(6):497–506.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Southey MC, Goldgar DE, Winqvist R, Pylkäs K, Couch F, Tischkowitz M, et al. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. J Med Genet. 2016;53(12):800–11. https://doi.org/10.1136/jmedgenet-2016-103839.

    Article  CAS  PubMed  Google Scholar 

  15. Bahcall OG. iCOGS collection provides a collaborative model. Nat Genet. 2013;45(4):343.

    Article  CAS  PubMed  Google Scholar 

  16. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013;45(4):353–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Couch FJ, Nathanson KL, Offit K. Two decades after BRCA: setting paradigms in personalized cancer care and prevention. Science. 2014;343(6178):1466–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Genetic/familial high-risk assessment: breast and ovarian. 2019. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf

  19. Oh JH, Noh DY, Choe KJ, Kang SB, Kim LS, Ro MS, et al. Germline mutation of BRCA1 gene in Korean breast and Overian cancer patients. Cancer Res Treat. 1995;27(6):1061–70.

    Google Scholar 

  20. Han SA, Park SK, Ahn SH, Son BH, Lee MH, Choi DH, et al. The breast and ovarian cancer risks in Korea due to inherited mutations in BRCA1 and BRCA2: a preliminary report. J Breast Cancer. 2009;12:92–9.

    Article  Google Scholar 

  21. Kang E, Kim SW. The korean hereditary breast cancer study: review and future perspectives. J Breast Cancer. 2013;16(3):245–53.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Han SA, Kim SW, Kang E, Park SK, Ann SH. The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean hereditary breast cancer study. Fam Cancer. 2012;12(1):75–81.

    Article  CAS  Google Scholar 

  23. Son BH, Ahn SH, Kim SW, Kang E, Park SK, Lee MH, et al. Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean hereditary breast cancer (KOHBRA) study. Breast Cancer Res Treat. 2012;133(3):1143–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Moynahan ME, Chiu JW, Koller BH, Jasin M. Brca1 controls homology-directed DNA repair. Mol Cell. 1999;4(4):511–8.

    Article  CAS  PubMed  Google Scholar 

  25. Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, et al. Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature. 2002;420(6913):287–93.

    Article  CAS  PubMed  Google Scholar 

  26. Lynch HT, Krush AJ. Carcinoma of the breast and ovary in three families. Surg Gynecol Obstet. 1971;133(4):644–8.

    CAS  PubMed  Google Scholar 

  27. Friedman LS, Ostermeyer EA, Lynch ED, Szabo CI, Anderson LA, Dowd P, et al. The search for BRCA1. Cancer Res. 1994;54(24):6374–82.

    CAS  PubMed  Google Scholar 

  28. Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93(21):1633–7.

    Article  CAS  PubMed  Google Scholar 

  29. Meijers-Heijboer H, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001;345(3):159–64.

    Article  CAS  PubMed  Google Scholar 

  30. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA. Van't veer L, Garber JE, et al. prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346(21):1616–22.

    Article  PubMed  Google Scholar 

  31. Kirova YM, Savignoni A, Sigal-Zafrani B, de La Rochefordiere A, Salmon RJ, This P, et al. Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature. Breast Cancer Res Treat. 2010;120(1):119–26.

    Article  PubMed  Google Scholar 

  32. Offit K, Kohut K, Clagett B, Wadsworth EA, Lafaro KJ, Cummings S, et al. Cancer genetic testing and assisted reproduction. J Clin Oncol. 2006;24(29):4775–82.

    Article  PubMed  Google Scholar 

  33. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Supreme court strikes down brca gene patent. 2013. https://abcnews.go.com/Politics/supreme-court-strikes-brca-gene-patent/story?id=19392299

  35. Kang E, Seong MW, Park SK, Lee JW, Lee J, Kim LS, et al. The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean hereditary breast cancer (KOHBRA) study. Breast Cancer Res Treat. 2015;151(1):157–68.

    Article  CAS  PubMed  Google Scholar 

  36. Birch JM, Blair V, Kelsey AM, Evans DG, Harris M, Tricker KJ, et al. Cancer phenotype correlates with constitutional TP53 genotype in families with the li-Fraumeni syndrome. Oncogene. 1998;17(9):1061–8.

    Article  CAS  PubMed  Google Scholar 

  37. Prochazkova K, Foretova L, Sedlacek Z. A rare tumor and an ethical dilemma in a family with a germline TP53 mutation. Cancer Genet Cytogenet. 2008;180(1):65–9.

    Article  CAS  PubMed  Google Scholar 

  38. Bougeard G, Renaux-Petel M, Flaman JM, Charbonnier C, Fermey P, Belotti M, et al. Revisiting li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol. 2015;33(21):2345–52.

    Article  CAS  PubMed  Google Scholar 

  39. Bennett KL, Mester J, Eng C. Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. JAMA. 2010;304(24):2724–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Daniell J, Plazzer JP, Perera A, Macrae F. An exploration of genotype-phenotype link between Peutz-Jeghers syndrome and STK11: a review. Fam Cancer. 2018;17(3):421–7.

    Article  CAS  PubMed  Google Scholar 

  41. Han SA, Park SK, Ahn SH, Lee MH, Noh DY, Kim LS, et al. The Korean hereditary breast cancer (KOHBRA) study: protocols and interim report. Clin Oncol (R Coll Radiol). 2011;23(7):434–41.

    Article  Google Scholar 

  42. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25(11):1329–33.

    Article  PubMed  Google Scholar 

  43. Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR, et al. A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res. 2004;6(1):R8–r17.

    Article  CAS  PubMed  Google Scholar 

  44. El-Tamer M, Russo D, Troxel A, Bernardino LP, Mazziotta R, Estabrook A, et al. Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann Surg Oncol. 2004;11(2):157–64.

    Article  PubMed  Google Scholar 

  45. Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med. 2007;357(2):115–23.

    Article  CAS  PubMed  Google Scholar 

  46. Lee EH, Park SK, Park B, Kim SW, Lee MH, Ahn SH, et al. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res Treat. 2010;122(1):11–25.

    Article  CAS  PubMed  Google Scholar 

  47. Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 2002;20(6):1480–90.

    Article  CAS  PubMed  Google Scholar 

  48. Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet. 1998;62(1):145–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Antoniou AC, Pharoah PP, Smith P, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer. 2004;91(8):1580–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Evans DG, Lalloo F, Wallace A, Rahman N. Update on the Manchester scoring system for BRCA1 and BRCA2 testing. J Med Genet. 2005;42(7):e39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kurian AW, Gong GD, Chun NM, Mills MA, Staton AD, Kingham KE, et al. Performance of BRCA1/2 mutation prediction models in Asian Americans. J Clin Oncol. 2008;26(29):4752–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kang E, Park SK, Yang JJ, Park B, Lee MH, Lee JW, et al. Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients. Breast Cancer Res Treat. 2012;134(3):1189–97.

    Article  CAS  PubMed  Google Scholar 

  53. Kim KS, Kim S, Han SA, Kang E, Jeon YT, Ha T-H, et al. Contralateral prophylactic mastectomy and prophylactic Salphingo-oophorectomy in a BRCA1-positive breast cancer patient: a case report. J Breast Cancer. 2008;11(4):218–22.

    Article  Google Scholar 

  54. Choi M-Y, Lee JE, Kim S-W, Lee SK, Hur SM, Kim S, et al. Incidental detection of ductal carcinoma in situ of the breast from bilateral prophylactic mastectomy of asymptomatic BRCA2 mutation carrier: a case report. J Breast Cancer. 2010;13(3):311–7.

    Article  Google Scholar 

  55. Kim D, Kang E, Hwang E, Sun Y, Hwang Y, Yom CK, et al. Factors affecting the decision to undergo risk-reducing salpingo-oophorectomy among women with BRCA gene mutation. Fam Cancer. 2013;12(4):621–8.

    Article  CAS  PubMed  Google Scholar 

  56. Ryu JM, Choi HJ, Kim I, Nam SJ, Kim SW, Yu J, et al. Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. Breast Cancer Res Treat. 2019;173(2):385–95.

    Article  CAS  PubMed  Google Scholar 

  57. Kim HC, Lee JY, Sung H, Choi JY, Park SK, Lee KM, et al. A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul breast cancer study. Breast Cancer Res. 2012;14(2):R56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Long J, Cai Q, Sung H, Shi J, Zhang B, Choi JY, et al. Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. PLoS Genet. 2012;8(2):e1002532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zheng W, Zhang B, Cai Q, Sung H, Michailidou K, Shi J, et al. Common genetic determinants of breast-cancer risk in east Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls. Hum Mol Genet. 2013;22(12):2539–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kyung Hee University, School of Medicine, Seoul, South Korea

    Sang-Ah Han

  2. Daerim St.Mary’s Hospital, Seoul, South Korea

    Sung-Won Kim

Authors
  1. Sang-Ah Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung-Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgery, College of Medicine, Seoul National University, Seoul, Korea (Republic of)

    Dong-Young Noh

  2. College of Medicine, Seoul National University College of Medicine, Seoul, Korea (Republic of)

    Wonshik Han

  3. Graduate School of Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Masakazu Toi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Han, SA., Kim, SW. (2021). BRCA and Breast Cancer-Related High-Penetrance Genes. In: Noh, DY., Han, W., Toi, M. (eds) Translational Research in Breast Cancer. Advances in Experimental Medicine and Biology, vol 1187. Springer, Singapore. https://doi.org/10.1007/978-981-32-9620-6_25

Download citation

Publish with us

Policies and ethics

Search

Navigation