Skip to main content

Advertisement

SpringerLink
Log in

The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The Korean Hereditary Breast Cancer (KOHBRA) study was established to evaluate the prevalence and spectrum of BRCA1/2 mutations in Korean breast cancer patients at risk for hereditary breast and ovarian cancer. A total of 2953 subjects (2403 index patients and 550 family members of affected carriers) from 36 centers participated in this study between May 2007 and December 2013. All participants received genetic counseling and BRCA genetic testing. In total, 378 mutation carriers among 2403 index patients were identified. The prevalence of BRCA mutations in specific subgroups was as follows: 22.3 % (274/1228) for breast cancer patients with a family history of breast/ovarian cancers, 8.8 % (39/441) for patients with early-onset (<35 years) breast cancer without a family history, 16.3 % (34/209) for patients with bilateral breast cancer, 4.8 % (1/21) for male patients with breast cancer, and 37.5 % (3/8) for patients with both breast and ovarian cancer. From an analysis of the mutation spectrum, 63 BRCA1 and 90 BRCA2 different mutations, including 44 novel mutations, were identified. The c.7480 (p.Arg2494Ter) mutation in BRCA2 (10.1 %) was the most commonly identified in this cohort. The KOHBRA study is the largest cohort to identify BRCA mutation carriers in Asia. The results suggest that the prevalence of BRCA mutations in familial breast cancer patients is similar to that among Western cohorts. However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kim Z, Min SY, Yoon CS, Lee HJ, Lee JS, Youn HJ, Park HK, Noh DY, Hur MH (2014) The basic facts of korean breast cancer in 2011: results of a nationwide survey and breast cancer registry database. J Breast Cancer 17(2):99–106

    Article  PubMed Central  PubMed  Google Scholar 

  2. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M (2010) Genetic susceptibility to breast cancer. Mol Oncol 4(3):174–191

    Article  CAS  PubMed  Google Scholar 

  3. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266(5182):66–71

    Article  CAS  PubMed  Google Scholar 

  4. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378(6559):789–792

    Article  CAS  PubMed  Google Scholar 

  5. Fackenthal JD, Olopade OI (2007) Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer 7(12):937–948

    Article  CAS  PubMed  Google Scholar 

  6. Oh JH, Noh DY, Choe KJ, Kang SB, Kim LS, Ro MS, Paik NS, Yang DH, Oh SM, Lee SN, Park JG (1995) Germline mutation of BRCA1 gene in Korean breast and overian cancer patients. Cancer Res Treat 27(6):1061–1070

    Google Scholar 

  7. Han SA, Kim SW, Kang E, Park SK, Ahn SH, Lee MH, Nam SJ, Han W, Bae YT, Kim HA, Cho YU, Chang MC, Paik NS, Hwang KT, Kim SJ, Noh DY, Choi DH, Noh WC, Kim LS, Kim KS, Suh YJ, Lee JE, Jung Y, Moon BI, Yang JH, Son BH, Yom CK, Kim SY, Lee H, Jung SH (2013) The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study. Fam Cancer 12(1):75–81

    Article  CAS  PubMed  Google Scholar 

  8. Son BH, Ahn SH, Kim SW, Kang E, Park SK, Lee MH, Noh WC, Kim LS, Jung Y, Kim KS, Noh DY, Moon BI, Suh YJ, Lee JE, Choi DH, Kim SY, Jung SH, Yom CK, Lee H, Yang JH (2012) 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 133(3):1143–1152

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Moyer VA (2014) Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 160(4):271–281

    Article  PubMed  Google Scholar 

  10. Gadzicki D, Evans DG, Harris H, Julian-Reynier C, Nippert I, Schmidtke J, Tibben A, van Asperen CJ, Schlegelberger B (2011) Genetic testing for familial/hereditary breast cancer-comparison of guidelines and recommendations from the UK, France, the Netherlands and Germany. J Community Genet 2(2):53–69

    Article  PubMed Central  PubMed  Google Scholar 

  11. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility (2003). J Clin Oncol 21 (12):2397-2406

  12. Han SA, Park SK, Ahn SH, Lee MH, Noh DY, Kim LS, Noh WC, Jung Y, Kim KS, Kim SW (2011) The Korean Hereditary Breast Cancer (KOHBRA) study: protocols and interim report. Clin Oncol (R Coll Radiol) 23(7):434–441

    Article  Google Scholar 

  13. Szabo CI, King MC (1997) Population genetics of BRCA1 and BRCA2. Am J Hum Genet 60(5):1013–1020

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Nat Cancer Inst 91(11):943–949

    Article  CAS  PubMed  Google Scholar 

  15. Malone KE, Daling JR, Neal C, Suter NM, O’Brien C, Cushing-Haugen K, Jonasdottir TJ, Thompson JD, Ostrander EA (2000) Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer 88(6):1393–1402

    Article  CAS  PubMed  Google Scholar 

  16. Hamann U, Liu X, Bungardt N, Ulmer HU, Bastert G, Sinn HP (2003) Similar contributions of BRCA1 and BRCA2 germline mutations to early-onset breast cancer in Germany. Eur J Hum Genet 11(6):464–467

    Article  CAS  PubMed  Google Scholar 

  17. Phuah SY, Looi LM, Hassan N, Rhodes A, Dean S, Taib NA, Yip CH, Teo SH (2012) Triple-negative breast cancer and PTEN (phosphatase and tensin homologue) loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer. Breast Cancer Res 14(6):R142

    Article  PubMed Central  PubMed  Google Scholar 

  18. Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, Brooks KA, Cohen S, Tenenholz B, Desai D, Zandvakili I, Royer R, Li S, Narod SA (2009) The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer 9:86

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Tai YC, Domchek S, Parmigiani G, Chen S (2007) Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 99(23):1811–1814

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Evans DG, Susnerwala I, Dawson J, Woodward E, Maher ER, Lalloo F (2010) Risk of breast cancer in male BRCA2 carriers. J Med Genet 47(10):710–711

    Article  CAS  PubMed  Google Scholar 

  21. Breast cancer incidence statistics. (2014) Cancer Research UK. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/uk-breast-cancer-incidence-statistics. Accessed 24 September 2014

  22. What are the key statistics about breast cancer in men? (2014) American Cancer society. http://www.cancer.org/cancer/breastcancerinmen/detailedguide/breast-cancer-in-men-key-statistics. Accessed 24 September 2014

  23. Basham VM, Lipscombe JM, Ward JM, Gayther SA, Ponder BA, Easton DF, Pharoah PD (2002) BRCA1 and BRCA2 mutations in a population-based study of male breast cancer. Breast Cancer Res 4(1):R2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Ding YC, Steele L, Kuan CJ, Greilac S, Neuhausen SL (2011) Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat 126(3):771–778

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Couch FJ, Farid LM, DeShano ML, Tavtigian SV, Calzone K, Campeau L, Peng Y, Bogden B, Chen Q, Neuhausen S, Shattuck-Eidens D, Godwin AK, Daly M, Radford DM, Sedlacek S, Rommens J, Simard J, Garber J, Merajver S, Weber BL (1996) BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nat Genet 13(1):123–125

    Article  CAS  PubMed  Google Scholar 

  26. Friedman LS, Gayther SA, Kurosaki T, Gordon D, Noble B, Casey G, Ponder BA, Anton-Culver H (1997) Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population. Am J Hum Genet 60(2):313–319

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Ahn SH, Son BH, Yoon KS, Noh DY, Han W, Kim SW, Lee ES, Park HL, Hong YJ, Choi JJ, Moon SY, Kim MJ, Kim KH, Kwak BS, Cho DY (2007) BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett 245(1–2):90–95

    Article  CAS  PubMed  Google Scholar 

  28. Kim H, Cho DY, Choi DH, Choi SY, Shin I, Park W, Huh SJ, Han SH, Lee MH, Ahn SH, Son BH, Kim SW, Haffty BG (2012) Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat 134(3):1315–1326

    Article  CAS  PubMed  Google Scholar 

  29. Seong MW, Cho S, Noh DY, Han W, Kim SW, Park CM, Park HW, Kim SY, Kim JY, Park SS (2009) Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation. Clin Genet 76(2):152–160

    Article  CAS  PubMed  Google Scholar 

  30. Kauff ND, Perez-Segura P, Robson ME, Scheuer L, Siegel B, Schluger A, Rapaport B, Frank TS, Nafa K, Ellis NA, Parmigiani G, Offit K (2002) Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. J Med Genet 39(8):611–614

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Puget N, Stoppa-Lyonnet D, Sinilnikova OM, Pages S, Lynch HT, Lenoir GM, Mazoyer S (1999) Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. Cancer Res 59(2):455–461

    CAS  PubMed  Google Scholar 

  32. Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, Roach KC, Mandell J, Lee MK, Ciernikova S, Foretova L, Soucek P, King MC (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295(12):1379–1388

    Article  CAS  PubMed  Google Scholar 

  33. Gad S, Caux-Moncoutier V, Pages-Berhouet S, Gauthier-Villars M, Coupier I, Pujol P, Frenay M, Gilbert B, Maugard C, Bignon YJ, Chevrier A, Rossi A, Fricker JP, Nguyen TD, Demange L, Aurias A, Bensimon A, Stoppa-Lyonnet D (2002) Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families. Oncogene 21(44):6841–6847

    Article  CAS  PubMed  Google Scholar 

  34. Hofmann W, Gorgens H, John A, Horn D, Huttner C, Arnold N, Scherneck S, Schackert HK (2003) Screening for large rearrangements of the BRCA1 gene in German breast or ovarian cancer families using semi-quantitative multiplex PCR method. Hum Mutat 22(1):103–104

    Article  PubMed  Google Scholar 

  35. Seong MW, Cho SI, Kim KH, Chung IY, Kang E, Lee JW, Park SK, Lee MH, Choi DH, Yom CK, Noh WC, Chang MC, Park SS, Kim SW (2014) A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients. BMC Cancer 14(1):645

    Article  PubMed Central  PubMed  Google Scholar 

  36. Han SH, Lee KR, Lee DG, Kim BY, Lee KE, Chung WS (2006) Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer. Clin Genet 70:496–501

    Article  PubMed  Google Scholar 

  37. Seo JH, Cho DY, Ahn SH, Yoon KS, Kang CS, Cho HM et al (2004) BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer. Hum Mutat 24:350

    Article  PubMed  Google Scholar 

  38. Kang HC, Kim IJ, Park JH, Kwon HJ, Won YJ, Heo SC et al (2002) Germline mutations of BRCA1 and BRCA2 in Korean breast and/or ovarian cancer families. Hum Mutat 20:235

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (#1020350). We thank all investigators of the KOHBRA study: Beom Seok Kwak, Byeong-Woo Park, Byung Ho Son, Byung-In Moon, Cha Kyong Yom, Chan Heun Park, Chan Seok Yoon, Chang Hyun Lee, Dae Sung Yoon, Dong-Young Noh, Doo Ho Choi, Eundeok Chang, Eun-Kyu Kim, Eunyoung Kang, Hae Kyung Lee, Hai-Lin Park, Hyde Lee, Hyeong-Gon Moon, Hyun-Ah Kim, Il-Kyun Lee, Jeong Eon Lee, Jihyoun Lee, Jong Won Lee, Jong-Han Yu, Joon Jeong, Jung Han Yoon, Jung-Hyun Yang, Keumhee Kwak, Ki-Tae Hwang, Ku Sang Kim, Lee Su Kim, Min Hee Hur, Min Ho Park, Min Hyuk Lee, Myung Chul Chang, Nam Sun Paik, Sang Ah Han, Sang Seol Jung, Sang Uk Woo, Se Jeong Oh, Sehwan Han, Sei Joong Kim, Sei-Hyun Ahn, Seok-Jin Nam, Seung Sang Ko, Sung Hoo Jung, Sung Soo Kang, Sung Yong Kim, Sung-Won Kim, Tae Hyun Kim, Tae Wan Won, Tae Woo Kang, Wonshik Han, Woo-Chul Noh, Yong Lai Park, Yongsik Jung, Young Jin Suh, Young Tae Bae, Young Up Cho, Young-Ik Hong, Sue K. Park, Yoon Joo Jung, Su Yun Choi, Young Bum Yoo, Soo-Jung Lee.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea

    Eunyoung Kang & Sung-Won Kim

  2. Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea

    Moon-Woo Seong

  3. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

    Sue K. Park

  4. Cancer Research Institute, Seoul National University, Seoul, Korea

    Sue K. Park

  5. Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Korea

    Sue K. Park

  6. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Jong Won Lee

  7. Department of Surgery, Soonchunhynag University Seoul Hospital, Seoul, Korea

    Jihyoun Lee

  8. Department of Surgery, Hallym University Sacred Heart Hospital, Anyang, Korea

    Lee Su Kim

  9. Department of Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea

    Jeong Eon Lee

  10. Department of Surgery, Soonchunhynag University Hospital, Cheonan, Korea

    Sung Yong Kim

  11. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea

    Joon Jeong

  12. Department of Surgery, KyungHee University Hospital, Seoul, Korea

    Sang Ah Han

Authors
  1. Eunyoung Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moon-Woo Seong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sue K. Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong Won Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jihyoun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lee Su Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeong Eon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sung Yong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sang Ah Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sung-Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Korean Hereditary Breast Cancer Study Group

Corresponding author

Correspondence to Sung-Won Kim.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, E., Seong, MW., Park, S.K. 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 151, 157–168 (2015). https://doi.org/10.1007/s10549-015-3377-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-015-3377-4

Keywords

Search

Navigation