Skip to main content

Advertisement

Springer Nature Link
Log in

Improved survival in BRCA2 carriers with ovarian cancer

  • Original Paper
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Objectives

The objective of this study was to investigate survival of ovarian cancer patients with BRCA1 and BRCA2 mutations compared to those without mutations in a population-based sample of incident epithelial ovarian cancer cases.

Methods

Follow-up for vital status was performed on a population-based sample of 232 women with incident epithelial ovarian cancer recruited between December 13, 2000 and September 30, 2003 in the Tampa Bay area. Survival analysis using Cox regression was performed on (1) all 232 cases and (2) the 209 invasive epithelial ovarian cancer cases. Results of the two analyses were similar, thus data involving the 209 invasive epithelial cancer cases are presented, as this was judged to be more clinically relevant.

Results

In the multivariate analysis, BRCA status and stage were statistically significant, and were adjusted for in the survival analysis model. The Kaplan–Meier method estimated expected survival at 4 years of 83% of BRCA2 carriers compared to 37% of BRCA1 carriers and 12% of non-carriers. There was a statistically significant difference between BRCA2 carriers and non-carriers (p = 0.013). No statistically significant survival differences were seen for BRCA1 carriers when compared with either BRCA2 carriers or non-carriers.

Conclusion

These data suggest that BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and non-carriers. The etiology of this possible survival advantage is currently unknown. Larger studies are needed to confirm these results and to clarify their etiology and clinical significance.

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

Access this article

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

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Whittemore AS (1994) Characteristics relating to ovarian cancer risk: implications for prevention and detection. Gynecol Oncol 55:S15–S19

    Article  PubMed  CAS  Google Scholar 

  2. Risch HA, McLaughlin JR, Cole DE et al (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 

  3. Pal T, Permuth-Wey J, Betts JA et al (2005) BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 104:2807–2816

    Article  PubMed  CAS  Google Scholar 

  4. Narod S, Ford D, Devilee P et al (1995) Genetic heterogeneity of breast–ovarian cancer revisited. Breast Cancer Linkage Consortium. Am J Hum Genet 57:957–958

    PubMed  CAS  Google Scholar 

  5. Frank TS, Manley SA, Olopade OI et al (1998) Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16:2417–2425

    PubMed  CAS  Google Scholar 

  6. Ford D, Easton DF, Bishop D (1994) Tea: risks of cancer in BRCA1 mutation carriers. Lancet 343:692–695

    Article  PubMed  CAS  Google Scholar 

  7. Struewing JP, Hartge P, Wacholder S et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408

    Article  PubMed  CAS  Google Scholar 

  8. Berchuck A, Heron KA, Carney ME et al (1998) Frequency of germline and somatic BRCA1 mutations in ovarian cancer. Clin Cancer Res 4:2433–2437

    PubMed  CAS  Google Scholar 

  9. Bjorge T, Lie AK, Hovig E et al (2004) BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case–control study. Br J Cancer 91:1829–1834

    Article  PubMed  CAS  Google Scholar 

  10. Khoo US, Ngan HY, Cheung AN et al (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 

  11. Malander S, Ridderheim M, Masback A et al (2004) One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden. Eur J Cancer 40:422–428

    Article  PubMed  CAS  Google Scholar 

  12. Matsushima M, Kobayashi K, Emi M et al (1995) Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation. Hum Mol Genet 4:1953–1956

    Article  PubMed  CAS  Google Scholar 

  13. Menkiszak J, Gronwald J, Gorski B et al (2003) Hereditary ovarian cancer in Poland. Int J Cancer 106:942–945

    Article  PubMed  CAS  Google Scholar 

  14. Modan B, Hartge P, Hirsh-Yechezkel G et al (2001) Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 345:235–240

    Article  PubMed  CAS  Google Scholar 

  15. Rafnar T, Benediktsdottir KR, Eldon BJ et al (2004) BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. Eur J Cancer 40:2788–2793

    Article  PubMed  CAS  Google Scholar 

  16. Rubin SC, Blackwood MA, Bandera C et al (1998) BRCA1, BRCA2 and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am J Obstet Gynecol 178:670–677

    Article  PubMed  CAS  Google Scholar 

  17. Sekine M, Nagata H, Tsuji S et al (2001) 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 7:3144–3150

    PubMed  CAS  Google Scholar 

  18. Stratton JF, Gayther SA, Russell P et al (1997) Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med 336:1125–1130

    Article  PubMed  CAS  Google Scholar 

  19. Takahashi H, Behbakht K, McGovern PE et al (1995) Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer Res 55:2998–3002

    PubMed  CAS  Google Scholar 

  20. Van Der Looij M, Szabo C, Besznyak I et al (2000) Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary. Int J Cancer 86:737–740

    Article  Google Scholar 

  21. Anton-Culver H, Cohen PF, Gildea ME et al (2000) Characteristics of BRCA1 mutations in a population-based case series of breast and ovarian cancer. Eur J Cancer 36:1200–1208

    Article  PubMed  CAS  Google Scholar 

  22. Majdak EJ, De Bock GH, Brozek I et al (2005) Prevalence and clinical correlations of BRCA1/BRCA2 unclassified variant carriers among unselected primary ovarian cancer cases—preliminary report. Eur J Cancer 41:143–150

    Article  PubMed  CAS  Google Scholar 

  23. American Cancer Society Inc (2005) Cancer facts & figures 2005. American Cancer Society Inc, Atlanta

  24. Mok SC, Chao J, Skates S et al (2001) Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 93:1458–1464

    Article  PubMed  CAS  Google Scholar 

  25. Schink JC (1999) Managing the care of patients with advanced ovarian cancer. Semin Oncol 26:59–61

    PubMed  CAS  Google Scholar 

  26. Schwartz PE, Taylor KJ (1995) Is early detection of ovarian cancer possible? Ann Med 27:519–528

    PubMed  CAS  Google Scholar 

  27. Taylor KJ, Schwartz PE (1994) Screening for early ovarian cancer. Radiology 192:1–10

    PubMed  CAS  Google Scholar 

  28. Greenlee RT, Hill-Harmon MB, Murray T et al (2001) Cancer statistics, 2001. CA Cancer J Clin 51:15–36

    Article  PubMed  CAS  Google Scholar 

  29. Cass I, Baldwin RL, Varkey T et al (2003) Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 97:2187–2195

    Article  PubMed  CAS  Google Scholar 

  30. Cortez D, Wang Y, Qin J et al (1999) Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286:1162–1166

    Article  PubMed  CAS  Google Scholar 

  31. Husain A, He G, Venkatraman ES et al (1998) BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II). Cancer Res 58:1120–1123

    PubMed  CAS  Google Scholar 

  32. Yang H, Jeffrey PD, Miller J et al (2002) BRCA2 function in DNA binding and recombination from a BRCA2–DSS1–ssDNA structure. Science 297:1837–1848

    Article  PubMed  CAS  Google Scholar 

  33. Aida H, Takakuwa K, Nagata H et al (1998) Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1. Clin Cancer Res 4:235–240

    PubMed  CAS  Google Scholar 

  34. Ben David Y, Chetrit A, Hirsh-Yechezkel G et al (2002) Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. J Clin Oncol 20:463–466

    Article  PubMed  CAS  Google Scholar 

  35. Boyd J, Sonoda Y, Federici MG et al (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 283:2260–2265

    Article  PubMed  CAS  Google Scholar 

  36. Buller RE, Anderson B, Connor JP et al (1993) Familial ovarian cancer. Gynecol Oncol 51:160–166

    Article  PubMed  CAS  Google Scholar 

  37. Rubin SC, Benjamin I, Behbakht K et al (1996) Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1. N Engl J Med 335:1413–1416

    Article  PubMed  CAS  Google Scholar 

  38. Johannsson OT, Ranstam J, Borg A et al (1998) Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J Clin Oncol 16:397–404

    PubMed  CAS  Google Scholar 

  39. Pharoah PD, Easton DF, Stockton DL et al (1999) Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. Cancer Res 59:868–871

    PubMed  CAS  Google Scholar 

  40. Ozols RF, Rubin SC, Thomas G et al (1997) Epithelial ovarian cancer. In Hoskins WJ, Perez CA, Young RC (eds) Principles and principles of gynecologic oncology. Lippincott-Raven Publishers, Philadelphia, p 958

    Google Scholar 

  41. World Health Organization (1979) WHO handbook for reporting results of cancer treatment. WHO, Geneva, Switzerland

    Google Scholar 

  42. Frank TS, Deffenbaugh AM, Reid JE et al (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20:1480–1490

    Article  PubMed  CAS  Google Scholar 

  43. Petrij-Bosch A, Peelen T, van Vliet M et al (1997) BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 17:341–345

    Article  PubMed  CAS  Google Scholar 

  44. The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographically diverse populations. The BRCA1 Exon 13 Duplication Screening Group. Am J Hum Genet 67:207–212, 2000

    Google Scholar 

  45. Unger MA, Nathanson KL, Calzone K et al (2000) Screening for genomic rearrangements in families with breast and ovarian cancer identifies BRCA1 mutations previously missed by conformation-sensitive gel electrophoresis or sequencing. Am J Hum Genet 67:841–850

    Article  PubMed  CAS  Google Scholar 

  46. Rohlfs EM, Puget N, Graham ML et al (2000) An Alu-mediated 7.1 kb deletion of BRCA1 exons 8 and 9 in breast and ovarian cancer families that results in alternative splicing of exon 10. Genes Chromosomes Cancer 28:300–307

    Article  PubMed  CAS  Google Scholar 

  47. Ward BC, Hendrikson CA, Gaglio T et al (2002) Identification of a novel 26 kb deletion in BRCA1 haplotype pair analysis [abstract]. Am J Hum Genet 71:249

    Google Scholar 

  48. Rubin SC, Benjamin SC, Behbakht K et al (1997) Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA-1. N Engl J Med 335:1413–1416

    Article  Google Scholar 

Download references

Acknowledgments

The Tampa Bay Ovarian Cancer Study was supported by grant # DAMD 17-98-1-8659 from the Department of Defense. The ongoing Ovarian Cancer and Mismatch Repair Deficiency Study is supported by grant # R01CA111914-01 from the National Cancer Institute. We are grateful for the work of Cheryl Miree, M.S., Katie Shuler, Elizabeth Allen, A.R.N.P, Mary Reilly, R.N., and Dominique Garvin, A.R.N.P. for data abstraction. We would especially like to thank all of the women who participated in the Tampa Bay Ovarian Cancer Study.

Author information

Authors and Affiliations

  1. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC-CANCONT, Tampa, FL , 33612, USA

    Tuya Pal, Jenny Permuth-Wey & Rebecca Sutphen

  2. Biostatistics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Rachna Kapoor & Alan Cantor

  3. Department of Interdisciplinary Oncology, College of Medicine, The University of South Florida, Tampa, FL, USA

    Tuya Pal, Jenny Permuth-Wey, Alan Cantor & Rebecca Sutphen

  4. Department of Pediatrics, College of Medicine, All Children’s Hospital, The University of South Florida, St Petersburg, FL, USA

    Tuya Pal & Rebecca Sutphen

Authors
  1. Tuya Pal
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Jenny Permuth-Wey
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Rachna Kapoor
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Alan Cantor
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Rebecca Sutphen
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Jenny Permuth-Wey.

Additional information

Article precis

Based on a population-based sample of 232 ovarian cancer patients, BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and non-carriers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pal, T., Permuth-Wey, J., Kapoor, R. et al. Improved survival in BRCA2 carriers with ovarian cancer. Familial Cancer 6, 113–119 (2007). https://doi.org/10.1007/s10689-006-9112-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-006-9112-x

Keywords