Skip to main content

Advertisement

Log in

The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified

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

Abstract

To have an overview of the role of BRCA1 and BRCA2 genes among Chinese high-risk breast cancer patients, we analyzed 489 such high-risk breast cancer patients from four breast disease clinical centers in China, by using PCR-DHPLC or SSCP-DNA sequencing analysis. Allelotype analysis was done at five short tandem repeat (STR) markers in or adjacent to BRCA1 on the recurrent mutation carriers. For those analyzed both genes, 8.7% of early-onset breast cancer cases and 12.9% of familial breast cancer cases had a BRCA1 or BRCA2 mutation, as compared with the 26.1% of cases with both early-onset breast cancer and affected relatives. For those reporting malignancy family history other than breast/ovarian cancer, the prevalence of BRCA1/2 mutation is about 20.5%, and it was significantly higher than the patients only with family history of breast/ovarian cancer (P = 0.02). The family history of ovarian cancer (26.7% vs. 11.9%) and stomach cancer (23.8% vs. 11.8%) doubled the incidence of BRCA1/2, but the difference did not reach the statistical significance. Two recurrent mutations in BRCA1, 1100delAT and 5589del8, were identified. The recurrent mutations account for 34.8% BRCA1 mutations in our series. Similar allelotypes were detected in most STR status for those harboring the same mutations. The BRCA1 associated tumors were more likely to exhibit a high tumor grade, negative C-erbB-2/neu status and triple negative (ER, PgR and C-erbB-2/neu negative) status (P < 0.05). We recommended the BRCA1 and BRCA2 genetic analysis could be done for high-risk breast cancer patient in Chinese population, especially for those with both early-onset breast cancer and affected relatives. There may be some degree of shared ancestry for the two recurrent BRCA1 mutations in Chinese.

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

Access this article

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. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Claus EB, Schildkraut JM, Thompson WD, Risch NJ (1996) The genetic attributable risk of breast and ovarian cancer. Cancer 77:2318–2324

    Article  PubMed  CAS  Google Scholar 

  3. 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 62:676–689

    CAS  Google Scholar 

  4. Weitzel JN (1999) Genetic cancer risk assessment. Putting it all together. Cancer 86:2483–2492

    CAS  Google Scholar 

  5. (2003) American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 21:2397–2406

  6. Daly MB, Axilbund JE, Bryant E, Buys S, Eng C, Friedman S, Esserman LJ, Farrell CD, Ford JM, Garber JE, Jeter JM, Kohlmann W, Lynch PM, Marcom PK, Nabell LM, Offit K, Osarogiagbon RU, Pasche B, Reiser G, Sutphen R, Weitzel JN (2005) Genetic/familial high-risk assessment: breast and ovarian, version 1.2006. National Comprehensive Cancer Network, Inc., Jenkintown

  7. Zhi X, Szabo C, Chopin S, Suter N, Wang QS, Ostrander EA, Sinilnikova OM, Lenoir GM, Goldgar D, Shi YR (2002) BRCA1 and BRCA2 sequence variants in Chinese breast cancer families. Hum Mutat 20:474

    Article  PubMed  Google Scholar 

  8. Hu Z, Wu J, Liu CH, Lu JS, Luo JM, Han QX, Shen ZZ, Shao ZM (2003) The analysis of BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives. Hum Mutat 22:104

    Article  PubMed  CAS  Google Scholar 

  9. Li N, Zhang X, Cai Y, Xu X, Zhang L, Pan KF, Wu LY, Wang MR (2006) BRCA1 germline mutations in Chinese patients with hereditary breast and ovarian cancer. Int J Gynecol Cancer 16(Suppl 1):172–178

    Article  PubMed  Google Scholar 

  10. Song CG, Hu Z, Wu J, Luo JM, Shen ZZ, Huang W, Shao ZM (2006) The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer. J Cancer Res Clin Oncol 132:617–626

    Article  PubMed  CAS  Google Scholar 

  11. Neuhausen SL, Mazoyer S, Friedman L, Stratton M, Offit K, Caligo A, Tomlinson G, Cannon-Albright L, Bishop T, Kelsell D, Solomon E, Weber B, Couch F, Struewing J, Tonin P, Durocher F, Narod S, Skolnick MH, Lenoir G, Serova O, Ponder B, Stoppa-Lyonnet D, Easton D, King MC, Goldgar DE (1996) Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am J Hum Genet 58:271–280

    PubMed  CAS  Google Scholar 

  12. FitzGerald MG, MacDonald DJ, Krainer M, Hoover I, O’Neil E, Unsal H, Silva-Arrieto S, Finkelstein DM, Beer-Romero P, Englert C, Sgroi DC, Smith BL, Younger JW, Garber JE, Duda RB, Mayzel KA, Isselbacher KJ, Friend SH, Haber DA (1996) Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med 334:143–149

    Article  PubMed  CAS  Google Scholar 

  13. Gal I, Gershoni Baruch R, Haber D, Dagan E, Eisenberg-Barzilai S, Zidan J, Friedman E (2004) The 1100delAT BRCA1 and the 8765delAG BRCA2 mutations: occurrence in high-risk non-Ashkenazi Jews and haplotype comparison of Jewish and non-Jewish carriers. Fam Cancer 3:11–14

    Article  PubMed  CAS  Google Scholar 

  14. De Benedetti VM, Radice P, Pasini B, Stagi L, Pensotti V, Mondini P, Manoukian S, Conti A, Spatti G, Rilke F, Pierotti MA (1998) Characterization of ten novel and 13 recurring BRCA1 and BRCA2 germline mutations in Italian breast and/or ovarian carcinoma patients. Mutations in brief no. 178. Online. Hum Mutat 12:215

    Google Scholar 

  15. Breast Cancer Information Core http://research.nhgri.nih.gov/bic/

  16. Suter NM, Ray RM, Hu YW, Lin MG, Porter P, Gao DL, Zaucha RE, Iwasaki LM, Sabacan LP, Langlois MC, Thomas DB, Ostrander EA (2004) BRCA1 and BRCA2 mutations in women from Shanghai China. Cancer Epidemiol Biomarkers Prev 13:181–189

    Article  PubMed  CAS  Google Scholar 

  17. Choi DH, Lee MH, Bale AE, Carter D, Haffty BG (2004) Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. J Clin Oncol 22:1638–1645

    Article  PubMed  CAS  Google Scholar 

  18. 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 266:66–71

    Article  PubMed  CAS  Google Scholar 

  19. 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 378:789–792

    Article  PubMed  CAS  Google Scholar 

  20. Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A (2001) Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst 93:1215–1223

    Article  PubMed  CAS  Google Scholar 

  21. Nanda R, Schumm LP, Cummings S, Fackenthal JD, Sveen L, Ademuyiwa F, Cobleigh M, Esserman L, Lindor NM, Neuhausen SL, Olopade OI (2005) Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. JAMA 294:1925–1933

    Article  PubMed  CAS  Google Scholar 

  22. 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 91:1241–1247

    Article  PubMed  CAS  Google Scholar 

  23. Ikeda N, Miyoshi Y, Yoneda K, Shiba E, Sekihara Y, Kinoshita M, Noguchi S (2001) Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer 91:83–88

    Article  PubMed  CAS  Google Scholar 

  24. Sng JH, Chang J, Feroze F, Rahman N, Tan W, Lim S, Lehnert M, van der Pool S, Wong J (2000) The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives. Br J Cancer 82:538–542

    Article  PubMed  CAS  Google Scholar 

  25. Li SS, Tseng HM, Yang TP, Liu CH, Teng SJ, Huang HW, Chen LM, Kao HW, Chen JH, Tseng JN, Chen A, Hou MF, Huang TJ, Chang HT, Mok KT, Tsai JH (1999) Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan. Hum Genet 104:201–204

    Article  PubMed  CAS  Google Scholar 

  26. Thompson D, Easton DF (2002) Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94:1358–1365

    PubMed  CAS  Google Scholar 

  27. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE (1994) Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343:692–695

    CAS  Google Scholar 

  28. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94:1365–1372

    PubMed  CAS  Google Scholar 

  29. Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, Tulinius H, Ogmundsdottir HM, Eyfjord JE (1996) A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet 13:117–119

    Article  PubMed  CAS  Google Scholar 

  30. (1999) Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst 91:1310–1316

  31. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68:700–710

    Article  PubMed  CAS  Google Scholar 

  32. Lorenzo Bermejo J, Hemminki K (2004) Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing. Ann Oncol 15:1834–1841

    Article  PubMed  CAS  Google Scholar 

  33. Armes JE, Venter DJ (2002) The pathology of inherited breast cancer. Pathology 34:309–314

    Article  PubMed  Google Scholar 

  34. Ahn SH, Hwang UK, Kwak BS, Yoon HS, Ku BK, Kang HJ, Kim JS, Ko BK, Ko CD, Yoon KS, Cho DY, Kim JS, Son BH (2004) Prevalence of BRCA1 and BRCA2 mutations in Korean breast cancer patients. J Korean Med Sci 19:269–274

    Article  PubMed  CAS  Google Scholar 

  35. 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 Natl Cancer Inst 91:943–949

    Article  PubMed  CAS  Google Scholar 

  36. Klein B, Weirich G, Brauch H (2001) DHPLC-based germline mutation screening in the analysis of the VHL tumor suppressor gene: usefulness and limitations. Hum Genet 108:376–384

    Article  PubMed  CAS  Google Scholar 

  37. Xiao W, Oefner PJ (2001) Denaturing high-performance liquid chromatography: a review. Hum Mutat 17:439–474

    Article  PubMed  CAS  Google Scholar 

  38. Tournier I, Paillerets BB, Sobol H, Stoppa-Lyonnet D, Lidereau R, Barrois M, Mazoyer S, Coulet F, Hardouin A, Chompret A, Lortholary A, Chappuis P, Bourdon V, Bonadona V, Maugard C, Gilbert B, Nogues C, Frebourg T, Tosi M (2004) Significant contribution of germline BRCA2 rearrangements in male breast cancer families. Cancer Res 64:8143–8147

    Article  PubMed  CAS  Google Scholar 

  39. Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drusedau M, Hogervorst FB, Hageman S, Arts PJ, Ligtenberg MJ, Meijers-Heijboer H, Klijn JG, Vasen HF, Cornelisse CJ, van ‘t Veer LJ, Bakker E, van Ommen GJ, Devilee P (1997) BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 17:341–345

    Article  PubMed  CAS  Google Scholar 

  40. Berry DA (2001) Role of population-based studies in assessing genetic cancer risk. J Natl Cancer Inst 93:1188–1189

    Article  PubMed  CAS  Google Scholar 

  41. Tonin P, Serova O, Lenoir G, Lynch H, Durocher F, Simard J, Morgan K, Narod S (1995) BRCA1 mutations in Ashkenazi Jewish women. Am J Hum Genet 57:189

    PubMed  CAS  Google Scholar 

  42. Tonin P, Weber B, Offit K, Couch F, Rebbeck TR, Neuhausen S, Godwin AK, Daly M, Wagner-Costalos J, Berman D, Grana G, Fox E, Kane MF, Kolodner RD, Krainer M, Haber DA, Struewing JP, Warner E, Rosen B, Lerman C, Peshkin B, Norton L, Serova O, Foulkes WD, Garber JE et al (1996) Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2:1179–1183

    Article  PubMed  CAS  Google Scholar 

  43. Andersen TI, Borresen AL, Moller P (1996) A common BRCA1 mutation in Norwegian breast and ovarian cancer families? Am J Hum Genet 59:486–487

    PubMed  CAS  Google Scholar 

  44. Tang NL, Pang CP, Yeo W, Choy KW, Lam PK, Suen M, Law LK, King WW, Johnson P, Hjelm M (1999) Prevalence of mutations in the BRCA1 gene among Chinese patients with breast cancer. J Natl Cancer Inst 91:882–885

    Article  PubMed  CAS  Google Scholar 

  45. Khoo US, Ngan HY, Cheung AN, Chan KY, Lu J, Chan VW, Lau S, Andrulis IL, Ozcelik H (2000) Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations. Hum Mutat 16:88–89

    Article  PubMed  CAS  Google Scholar 

  46. Khoo US, Chan KY, Cheung AN, Xue WC, Shen DH, Fung KY, Ngan HY, Choy KW, Pang CP, Poon CS, Poon AY, Ozcelik H (2002) Recurrent BRCA1 and BRCA2 germline mutations in ovarian cancer: a founder mutation of BRCA1 identified in the Chinese population. Hum Mutat 19:307–308

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported in part by the grants from National Natural Science Foundation of China (30371580, 30572109; to ZM. S.); Shanghai Science and Technology Committee (03J14019, 06DJ14004, 06DZ19504; to ZM. S.); Science Foundation for Young Investigator of Fudan University, (JKF159002; to Z. H.); National Basic Research Program of China (2006CB 910501; to ZM. S).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhi-Ming Shao.

Additional information

Wen-Feng Li and Zhen Hu have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, WF., Hu, Z., Rao, NY. et al. The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified. Breast Cancer Res Treat 110, 99–109 (2008). https://doi.org/10.1007/s10549-007-9708-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9708-3

Keywords

Navigation