Breast Cancer

, Volume 22, Issue 5, pp 462–468 | Cite as

Prevalence and differentiation of hereditary breast and ovarian cancers in Japan

  • Seigo Nakamura
  • Masato Takahashi
  • Mitsuhiro Tozaki
  • Takahiro Nakayama
  • Tadashi Nomizu
  • Yoshio Miki
  • Yoshie Murakami
  • Daisuke Aoki
  • Takuji Iwase
  • Seiichiro Nishimura
  • Hideko Yamauchi
  • Shozo Ohsumi
  • Shinichi Baba
  • Tadao Shimizu
Original Article
First Online:
Received:
Accepted:

Abstract

Background

We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan.

Materials and methods

Our study of BRCA1/2 collected data at eight institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March 2012.

Results

Among 260 proband cases, 46 (17.7 %) were positive for BRCA1, and 35 (13.5 %) were BRCA2-positive. Therefore, the total pathological mutation rate was 30.7 %. Pathology data after breast surgery were obtained from 37 cases of BRCA1 mutation, 23 (62.2 %) of which were triple negative (TN). On the other hand, 29 cases (82.9 %) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found two cases of large deletion detected by multiplex ligation-dependent probe amplification. One was an entire deletion of exon 20 and the lacked exons 1–9. TN with a family history of ovarian cancer was 11/20 (55 %). TN under 40-year-old (y.o.) 15/23 (65.2 %) and TN with one or more breast cancers in family history 17/32 (53.1 %) showed higher incidences of BRCA1 mutation.

Conclusion

Hereditary breast and ovarian cancer (HBOC) may have nearly the same prevalence in Japan as in the US or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to develop risk models for BRCA1/2 carriers in Japan.

Keywords

HBOC BRCA1 BRCA2 Triple negative L63X 
This is a preview of subscription content, log in to check access.

Notes

Conflict of interest

Seigo Nakamura has no conflict of interest. Masato Takahashi has no conflict of interest. Mitsuhiro Tozaki has no conflict of interest. Takahiro Nakayama has no conflict of interest. Tadashi Nomizu has no conflict of interest. Yoshio Miki received $30,000/year as a royalty for Breast Cancer Gene U-2090 from the University of Utah. Yoshie Murakami has no conflict of interest. Daisuke Aoki has no conflict of interest. Takuji Iwase has no conflict of interest. Seiichiro Nishimura has no conflict of interest. Hideko Yamauchi has no conflict of interest. Shozo Ohsumi has no conflict of interest. Shinichi Baba has no conflict of interest. Tadao Shimizu has no conflict of interest.

References

  1. 1.
    Miki Y, Swensen J, Shattuck-Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66–71.CrossRefPubMedGoogle Scholar
  2. 2.
    Risch HA, McLaughlin JR, Cole DE, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001;68:700–10.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Risch HA, McLaughlin JR, Cole DE, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98:1694–706.CrossRefPubMedGoogle Scholar
  4. 4.
    Loman N, Johannsson O, Kristoffersson U, et al. 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. 2001;93:1215–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Ikeda N, Miyoshi Y, Yoneda K, et al. Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer. 2001;91:83–8.CrossRefPubMedGoogle Scholar
  6. 6.
    NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian ver.1.2010 and ver.1.2011.Google Scholar
  7. 7.
    Frank TS, Manley SA, Olopade OI, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol. 1998;16:2417–25.PubMedGoogle Scholar
  8. 8.
    Schouten JP, McElgunn CJ, Waaijer R, et al. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002;30:e57.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Hogervorst FB, Nederlof PM, Gill JP, et al. Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res. 2003;63:1449–53.PubMedGoogle Scholar
  10. 10.
    Bunyan DJ, Eccles DM, Sillibourne J, et al. Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification. Br J Cancer. 2004;9:1155–9.CrossRefGoogle Scholar
  11. 11.
    Sugano K, Nakamura S, Ando J, et al. Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. Cancer Sci. 2008;99:1967–76.CrossRefPubMedGoogle Scholar
  12. 12.
    Young SR, Pilarski RT, Donenberg T, et al. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009;19:86.CrossRefGoogle Scholar
  13. 13.
    Fostira F, Tsitlaidou M, Papadimitriou C, et al. Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study. Breast Cancer Res Treat. 2012;134:353–62.CrossRefPubMedGoogle Scholar
  14. 14.
    Sekine M, Nagata H, Tsuji S, Japanese Familial Ovarian Cancer Study Group, et al. Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population. Clin Cancer Res. 2001;7:3144–50.PubMedGoogle Scholar
  15. 15.
    Bellosillo B, Tusquets I. Pitfalls and caveats in BRCA sequencing. Ultrastruct Pathol. 2006;30:229–35.CrossRefPubMedGoogle Scholar
  16. 16.
    Mazoyer S. Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat. 2005;25:415–22.CrossRefPubMedGoogle Scholar
  17. 17.
    Ticha I, Kleibl Z, Stribrna J, et al. Screening for genomic rearrangements in BRCA1 and BRCA2 genes in Czech high-risk breast/ovarian cancer patients: high proportion of population specific alterations in BRCA1 gene. Breast Cancer Res Treat. 2010;124:337–47.CrossRefPubMedGoogle Scholar
  18. 18.
    Sluiter MD, van Rensburg EJ. Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat. 2011;125:325–49.CrossRefPubMedGoogle Scholar
  19. 19.
    Engert S, Wappenschmidt B, Betz B, et al. MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: novel deletions, frequent involvement of exon 17, and occurrence in single early-onset cases. Hum Mutat. 2008;29:948–58.CrossRefPubMedGoogle Scholar
  20. 20.
    Ready K, Litton JK, Arun BK. Clinical application of breast cancer risk assessment models. Future Oncol. 2010;6:355–65.CrossRefPubMedGoogle Scholar
  21. 21.
    Amir E, Freedman OC, Seruga B, et al. Assessing women at high risk of breast cancer: a review of risk assessment models. J Natl Cancer Inst. 2010;102:680–91.CrossRefPubMedGoogle Scholar
  22. 22.
    Kwong A, Wong CH, Suen DT, et al. Accuracy of BRCA1/2 mutation prediction models for different ethnicities and genders: experience in a southern Chinese cohort. World J Surg. 2012;36:702–13.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Kang E, Park SK, Yang JJ, Korean Breast Cancer Society, et al. Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients. Breast Cancer Res Treat. 2012;134:1189–97.CrossRefPubMedGoogle Scholar
  24. 24.
    Berry DA, Iversen ES Jr, Gudbjartsson DF, et al. BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol. 2002;20:2701–12.CrossRefPubMedGoogle Scholar
  25. 25.
    Lindor NM, McMaster ML, Lindor CJ, et al. Concise handbook of familial cancer susceptibility syndromes—second edition. J Natl Cancer Inst Monogr. 2008;38:1–93.PubMedGoogle Scholar
  26. 26.
    Garcia-Etienne CA, Barile M, Gentilini OD, et al. Breast-conserving surgery in BRCA1/2 mutation carriers: are we approaching an answer? Ann Surg Oncol. 2009;16:3380–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Kirova YM, Savignoni A, Sigal-Zafrani B, 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;120:119–26.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2013

Authors and Affiliations

  • Seigo Nakamura
    • 1
  • Masato Takahashi
    • 2
  • Mitsuhiro Tozaki
    • 3
  • Takahiro Nakayama
    • 4
  • Tadashi Nomizu
    • 5
  • Yoshio Miki
    • 6
  • Yoshie Murakami
    • 7
  • Daisuke Aoki
    • 8
  • Takuji Iwase
    • 9
  • Seiichiro Nishimura
    • 10
  • Hideko Yamauchi
    • 11
  • Shozo Ohsumi
    • 12
  • Shinichi Baba
    • 13
  • Tadao Shimizu
    • 14
  1. 1.Division of Breast Surgical Oncology, Department of SurgeryShowa University School of MedicineTokyoJapan
  2. 2.Department of Breast SurgeryHokkaido Cancer CenterSapporoJapan
  3. 3.Breast CenterKameda Medical CenterChibaJapan
  4. 4.Department of Breast and Endocrine SurgeryOsaka Medical Center for Cancer and Cardiovascular DiseaseOsakaJapan
  5. 5.Department of SurgeryHoshi General HospitalFukushimaJapan
  6. 6.Department of Genetic DiagnosisThe Cancer Institute Hospital of JFCRTokyoJapan
  7. 7.Department of Adult Health NursingToho UniversityTokyoJapan
  8. 8.Department of Obstetrics and GynecologyKeio University School of MedicineTokyoJapan
  9. 9.Breast Oncology CenterThe Cancer Institute Hospital of Japanese Foundation of Cancer ResearchTokyoJapan
  10. 10.Department of Breast SurgeryShizuoka Cancer CenterShizuokaJapan
  11. 11.Breast Surgical DepartmentSt.Luke’s International HospitalTokyoJapan
  12. 12.Breast OncologyShikoku Cancer CenterEhimeJapan
  13. 13.Breast Surgery DepartmentSagara HospitalKagoshimaJapan
  14. 14.Department of Breast SurgeryTokyo Women’s Medical University Medical Center EastTokyoJapan

Personalised recommendations