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Breast Cancer Research and Treatment

, Volume 152, Issue 3, pp 659–665 | Cite as

Breast cancer risk for Korean women with germline mutations in BRCA1 and BRCA2

  • Boyoung Park
  • James G. Dowty
  • Choonghyun Ahn
  • Aung K. Win
  • Sung-Won Kim
  • Min Hyuk Lee
  • Jong Won Lee
  • Eunyoung Kang
  • John L. Hopper
  • Sue K. Park
Epidemiology

Abstract

The average age-specific cumulative risk (penetrance) of breast cancer has been studied for BRCA1 and BRCA2 mutation carriers living in Western countries, but not for those living in East Asian countries where the population breast cancer incidence is lower. From 2007 to 2011, the Korean Hereditary Breast Cancer study identified 151 BRCA1 and 225 BRCA2 mutation-carrying families from family cancer clinics. We estimated the hazard ratio (HR) for female carriers relative to the population, and hence the penetrance, using a modified segregation analysis of cancer family histories conditioned on ascertainment. The breast cancer HR estimates [95 % confidence interval (CI)] for BRCA1 and BRCA2 mutation carriers were 18 (3–103) and 11 (5–27), respectively. The breast cancer penetrance estimates (95 % CI) to age 70 years were 49 % (11–98) and 35 % (16–65) for BRCA1 and BRCA2 mutation carriers, respectively. The breast cancer HR and penetrance estimates were similar for Korean and Western women (all P > 0.4). The point estimates of breast cancer penetrance were similar to age 50 years, though less for Korean carriers at older ages. Breast cancer risk for Korean and Western mutation carriers might reflect underlying population risks which in turn likely reflect differences in environmental and lifestyle factors. This raises the possibility of identifying modifiers of cancer risk for carriers with implications for prevention.

Keywords

Average cumulative risk BRCA1/2 mutation carrier Breast cancer risk Penetrance 

Notes

Acknowledgments

This study was supported by a Grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (#1020350 and #1420190).

References

  1. 1.
    Venkitaraman AR (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108(2):171–182CrossRefPubMedGoogle Scholar
  2. 2.
    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. doi: 10.1038/378789a0 CrossRefPubMedGoogle Scholar
  3. 3.
    Narod SA, Offit K (2005) Prevention and management of hereditary breast cancer. J Clin Oncol 23(8):1656–1663. doi: 10.1200/jco.2005.10.035 CrossRefPubMedGoogle Scholar
  4. 4.
    Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast cancer linkage consortium. Am J Hum Genet 56(1):265–271PubMedCentralPubMedGoogle Scholar
  5. 5.
    Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet 62(3):676–689PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Hopper JL, Southey MC, Dite GS, Jolley DJ, Giles GG, McCredie MR, Easton DF, Venter DJ (1999) Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Oncology 8(9):741–747Google Scholar
  7. 7.
    Levy-Lahad E, Friedman E (2007) Cancer risks among BRCA1 and BRCA2 mutation carriers. Br J Cancer 96(1):11–15. doi: 10.1038/sj.bjc.6603535 PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336(20):1401–1408. doi: 10.1056/nejm199705153362001 CrossRefPubMedGoogle Scholar
  9. 9.
    Warner E, Foulkes W, Goodwin P, Meschino W, Blondal J, Paterson C, Ozcelik H, Goss P, Allingham-Hawkins D, Hamel N, Di Prospero L, Contiga V, Serruya C, Klein M, Moslehi R, Honeyford J, Liede A, Glendon G, Brunet JS, Narod S (1999) Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 91(14):1241–1247CrossRefPubMedGoogle Scholar
  10. 10.
    Thorlacius S, Struewing JP, Hartge P, Olafsdottir GH, Sigvaldason H, Tryggvadottir L, Wacholder S, Tulinius H, Eyfjord JE (1998) Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352(9137):1337–1339CrossRefPubMedGoogle Scholar
  11. 11.
    Anglian Breast Cancer Study Group (2000) Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer 83(10):1301–1308. doi: 10.1054/bjoc.2000.1407 PubMedCentralCrossRefGoogle Scholar
  12. 12.
    Satagopan JM, Offit K, Foulkes W, Robson ME, Wacholder S, Eng CM, Karp SE, Begg CB (2001) The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomark Prev 10(5):467–473Google Scholar
  13. 13.
    Thompson D, Easton D (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68(2):410–419. doi: 10.1086/318181 PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Thompson D, Easton DF (2002) Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94(18):1358–1365CrossRefPubMedGoogle Scholar
  15. 15.
    Ding YC, McGuffog L, Healey S, Friedman E, Laitman Y, Paluch-Shimon S, Kaufman B, Liljegren A, Lindblom A, Olsson H, Kristoffersson U, Stenmark-Askmalm M, Melin B, Domchek SM, Nathanson KL, Rebbeck TR, Jakubowska A, Lubinski J, Jaworska K, Durda K, Gronwald J, Huzarski T, Cybulski C, Byrski T, Osorio A, Cajal TR, Stavropoulou AV, Benitez J, Hamann U, Rookus M, Aalfs CM, de Lange JL, Meijers-Heijboer HE, Oosterwijk JC, van Asperen CJ, Gomez Garcia EB, Hoogerbrugge N, Jager A, van der Luijt RB, Easton DF, Peock S, Frost D, Ellis SD, Platte R, Fineberg E, Evans DG, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Tischkowitz M, Godwin AK, Pathak H, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Barjhoux L, Leone M, Gauthier-Villars M, Caux-Moncoutier V, de Pauw A, Hardouin A, Berthet P, Dreyfus H, Ferrer SF, Collonge-Rame MA, Sokolowska J, Buys S, Daly M, Miron A, Terry MB, Chung W, John EM, Southey M, Goldgar D, Singer CF, Tea MK, Gschwantler-Kaulich D, Fink-Retter A, Hansen TV, Ejlertsen B, Johannsson OT, Offit K, Sarrel K, Gaudet MM, Vijai J, Robson M, Piedmonte MR, Andrews L, Cohn D, DeMars LR, DiSilvestro P, Rodriguez G, Toland AE, Montagna M, Agata S, Imyanitov E, Isaacs C, Janavicius R, Lazaro C, Blanco I, Ramus SJ, Sucheston L, Karlan BY, Gross J, Ganz PA, Beattie MS, Schmutzler RK, Wappenschmidt B, Meindl A, Arnold N, Niederacher D, Preisler-Adams S, Gadzicki D, Varon-Mateeva R, Deissler H, Gehrig A, Sutter C, Kast K, Nevanlinna H, Aittomaki K, Simard J, Spurdle AB, Beesley J, Chen X, Tomlinson GE, Weitzel J, Garber JE, Olopade OI, Rubinstein WS, Tung N, Blum JL, Narod SA, Brummel S, Gillen DL, Lindor N, Fredericksen Z, Pankratz VS, Couch FJ, Radice P, Peterlongo P, Greene MH, Loud JT, Mai PL, Andrulis IL, Glendon G, Ozcelik H, Gerdes AM, Thomassen M, Jensen UB, Skytte AB, Caligo MA, Lee A, Chenevix-Trench G, Antoniou AC, Neuhausen SL (2012) A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers. Cancer Epidemiol Biomark Prev 21(8):1362–1370. doi: 10.1158/1055-9965.epi-12-0229 CrossRefGoogle Scholar
  16. 16.
    Antoniou AC, Kuchenbaecker KB, Soucy P, Beesley J, Chen X, McGuffog L, Lee A, Barrowdale D, Healey S, Sinilnikova OM, Caligo MA, Loman N, Harbst K, Lindblom A, Arver B, Rosenquist R, Karlsson P, Nathanson K, Domchek S, Rebbeck T, Jakubowska A, Lubinski J, Jaworska K, Durda K, Zlowowcka-Perlowska E, Osorio A, Duran M, Andres R, Benitez J, Hamann U, Hogervorst FB, van Os TA, Verhoef S, Meijers-Heijboer HE, Wijnen J, Gomez Garcia EB, Ligtenberg MJ, Kriege M, Collee JM, Ausems MG, Oosterwijk JC, Peock S, Frost D, Ellis SD, Platte R, Fineberg E, Evans DG, Lalloo F, Jacobs C, Eeles R, Adlard J, Davidson R, Cole T, Cook J, Paterson J, Douglas F, Brewer C, Hodgson S, Morrison PJ, Walker L, Rogers MT, Donaldson A, Dorkins H, Godwin AK, Bove B, Stoppa-Lyonnet D, Houdayer C, Buecher B, de Pauw A, Mazoyer S, Calender A, Leone M, Bressac-de Paillerets B, Caron O, Sobol H, Frenay M, Prieur F, Ferrer SU, Mortemousque I, Buys S, Daly M, Miron A, Terry MU, Hopper JL, John EM, Southey M, Goldgar D, Singer CF, Fink-Retter A, Tea MK, Kaulich DU, Hansen TV, Nielsen FC, Barkardottir RB, Gaudet M, Kirchhoff T, Joseph V, Dutra-Clarke A, Offit K, Piedmonte M, Kirk J, Cohn D, Hurteau J, Byron J, Fiorica J, Toland AE, Montagna M, Oliani C, Imyanitov E, Isaacs C, Tihomirova L, Blanco I, Lazaro C, Teule A, Valle JD, Gayther SA, Odunsi K, Gross J, Karlan BY, Olah E, Teo SH, Ganz PA, Beattie MS, Dorfling CM, van Rensburg EU, Diez O, Kwong A, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Ditsch N, Arnold N, Heidemann S, Niederacher D, Preisler-Adams S, Gadzicki D, Varon-Mateeva R, Deissler H, Gehrig A, Sutter C, Kast K, Fiebig B, Schafer D, Caldes T, de la Hoya M, Nevanlinna H, Muranen TA, Lesperance B, Spurdle AB, Neuhausen SL, Ding YC, Wang X, Fredericksen Z, Pankratz VS, Lindor NM, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Bonanni B, Bernard L, Dolcetti R, Papi L, Ottini L, Radice P, Greene MH, Loud JT, Andrulis IL, Ozcelik H, Mulligan AU, Glendon G, Thomassen M, Gerdes AM, Jensen UB, Skytte AB, Kruse TA, Chenevix-Trench G, Couch FJ, Simard J, Easton DF (2012) Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. Breast Cancer Res BCR 14(1):R33. doi: 10.1186/bcr3121
  17. 17.
    Catucci I, Verderio P, Pizzamiglio S, Manoukian S, Peissel B, Zaffaroni D, Roversi G, Ripamonti CB, Pasini B, Barile M, Viel A, Giannini G, Papi L, Varesco L, Martayan A, Riboni M, Volorio S, Radice P, Peterlongo P (2011) The CASP8 rs3834129 polymorphism and breast cancer risk in BRCA1 mutation carriers. Breast Cancer Res Treat 125(3):855–860. doi: 10.1007/s10549-010-1068-8 CrossRefPubMedGoogle Scholar
  18. 18.
    Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) 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 72(5):1117–1130. doi: 10.1086/375033 PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646. doi: 10.1126/science.1088759 CrossRefPubMedGoogle Scholar
  20. 20.
    Iodice S, Barile M, Rotmensz N, Feroce I, Bonanni B, Radice P, Bernard L, Maisonneuve P, Gandini S (2010) Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer 46(12):2275–2284. doi: 10.1016/j.ejca.2010.04.018 CrossRefPubMedGoogle Scholar
  21. 21.
    Milne RL, Osorio A, Ramon y Cajal T, Baiget M, Lasa A, Diaz-Rubio E, de la Hoya M, Caldes T, Teule A, Lazaro C, Blanco I, Balmana J, Sanchez-Olle G, Vega A, Blanco A, Chirivella I, Esteban Cardenosa E, Duran M, Velasco E, Martinez de Duenas E, Tejada MI, Miramar MD, Calvo MT, Guillen-Ponce C, Salazar R, San Roman C, Urioste M, Benitez J (2010) Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 119(1):221–232. doi: 10.1007/s10549-009-0394-1 CrossRefPubMedGoogle Scholar
  22. 22.
    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 23(7):434–441. doi: 10.1016/j.clon.2010.11.007 CrossRefGoogle Scholar
  23. 23.
    Lange K, Weeks D, Boehnke M (1988) Programs for pedigree analysis: MENDEL, FISHER, and dGENE. Genet Epidemiol 5(6):471–472. doi: 10.1002/gepi.1370050611 CrossRefPubMedGoogle Scholar
  24. 24.
    Brohet RM, Velthuizen ME, Hogervorst FB, Meijers-Heijboer HE, Seynaeve C, Collee MJ, Verhoef S, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia E, Menko F, Oosterwijk JC, Devilee P, van’t Veer LJ, van Leeuwen FE, Easton DF, Rookus MA, Antoniou AC (2014) Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. J Med Genet 51(2):98–107. doi: 10.1136/jmedgenet-2013-101974 CrossRefPubMedGoogle Scholar
  25. 25.
    Milne RL, Osorio A, Cajal TR, Vega A, Llort G, de la Hoya M, Diez O, Alonso MC, Lazaro C, Blanco I, Sanchez-de-Abajo A, Caldes T, Blanco A, Grana B, Duran M, Velasco E, Chirivella I, Cardenosa EE, Tejada MI, Beristain E, Miramar MD, Calvo MT, Martinez E, Guillen C, Salazar R, San Roman C, Antoniou AC, Urioste M, Benitez J (2008) The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain. Clin Cancer Res 14(9):2861–2869. doi: 10.1158/1078-0432.ccr-07-4436 CrossRefPubMedGoogle Scholar
  26. 26.
    The Korea Central Cancer Registry, National Cancer Center (2012) Annual report of cancer statistics in Korea in 2010, Ministry of Health and WelfareGoogle Scholar
  27. 27.
    Park B, Ma SH, Shin A, Chang MC, Choi JY, Kim S, Han W, Noh DY, Ahn SH, Kang D, Yoo KY, Park SK (2013) Korean risk assessment model for breast cancer risk prediction. PLoS One 8(10):e76736. doi: 10.1371/journal.pone.0076736 PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Kang E, Park SK, Yang JJ, Park B, Lee MH, Lee JW, Suh YJ, Lee JE, Kim HA, Oh SJ, Kim SW (2012) Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients. Breast Cancer Res Treat 134(3):1189–1197. doi: 10.1007/s10549-012-2022-8 CrossRefPubMedGoogle Scholar
  29. 29.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333. doi: 10.1200/jco.2006.09.1066 PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Theis B, Boyd N, Lockwood G, Tritchler D (1994) Accuracy of family cancer history in breast cancer patients. Eur J Cancer Prev 3(4):321–327CrossRefPubMedGoogle Scholar
  31. 31.
    Ziogas A, Anton-Culver H (2003) Validation of family history data in cancer family registries. Am J Prev Med 24(2):190–198CrossRefPubMedGoogle Scholar
  32. 32.
    Ewens WJ, Shute NC (1986) A resolution of the ascertainment sampling problem. I. Theory. Theor Popul Biol 30(3):388–412CrossRefPubMedGoogle Scholar
  33. 33.
    Carayol J, Khlat M, Maccario J, Bonaiti-Pellie C (2002) Hereditary non-polyposis colorectal cancer: current risks of colorectal cancer largely over estimated. J Med Genet 39(5):335–339PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Carayol J, Bonaiti-Pellie C (2004) Estimating penetrance from family data using a retrospective likelihood when ascertainment depends on genotype and age of onset. Genet Epidemiol 27(2):109–117. doi: 10.1002/gepi.20007 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Boyoung Park
    • 1
    • 2
  • James G. Dowty
    • 3
  • Choonghyun Ahn
    • 4
    • 5
    • 6
  • Aung K. Win
    • 3
  • Sung-Won Kim
    • 7
  • Min Hyuk Lee
    • 8
  • Jong Won Lee
    • 9
  • Eunyoung Kang
    • 10
  • John L. Hopper
    • 3
    • 11
    • 12
  • Sue K. Park
    • 4
    • 5
    • 6
  1. 1.Graduate School of Cancer Science and PolicyNational Cancer CenterGoyangKorea
  2. 2.National Cancer Control InstituteNational Cancer CenterGoyangKorea
  3. 3.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthThe University of MelbourneParkvilleAustralia
  4. 4.Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
  5. 5.Cancer Research InstituteSeoul National UniversitySeoulKorea
  6. 6.Department of Biomedical ScienceSeoul National University Graduate SchoolSeoulKorea
  7. 7.Department of SurgeryDaerim-Sungmo HospitalSeoulKorea
  8. 8.Department of Surgery, College of MedicineSoonchunhyang UniversitySeoulKorea
  9. 9.Department of Surgery, College of MedicineUniversity of Ulsan and Asan Medical CenterSeoulKorea
  10. 10.Department of Surgery, Breast and Endocrine ServiceSeoul National University Bundang HospitalGyeonggi-doKorea
  11. 11.Department of Epidemiology, School of Public HealthSeoul National UniversitySeoulKorea
  12. 12.Institute of Health and EnvironmentSeoul National UniversitySeoulKorea

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