Skip to main content

Advertisement

SpringerLink
Log in

Electronically ascertained extended pedigrees in breast cancer genetic counseling

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

Abstract

A comprehensive pedigree, usually provided by the counselee and verified by medical records, is essential for risk assessment in cancer genetic counseling. Collecting the relevant information is time-consuming and sometimes impossible. We studied the use of electronically ascertained pedigrees (EGP). The study group comprised women (n = 1352) receiving HBOC genetic counseling between December 2006 and December 2016 at Landspitali in Iceland. EGP’s were ascertained using information from the population-based Genealogy Database and Icelandic Cancer Registry. The likelihood of being positive for the Icelandic founder BRCA2 pathogenic variant NM_000059.3:c.767_771delCAAAT was calculated using the risk assessment program Boadicea. We used this unique data to estimate the optimal size of pedigrees, e.g., those that best balance the accuracy of risk assessment using Boadicea and cost of ascertainment. Sub-groups of randomly selected 104 positive and 105 negative women for the founder BRCA2 PV were formed and Receiver Operating Characteristics curves compared for efficiency of PV prediction with a Boadicea score. The optimal pedigree size included 3° relatives or up to five generations with an average no. of 53.8 individuals (range 9–220) (AUC 0.801). Adding 4° relatives did not improve the outcome. Pedigrees including 3° relatives are difficult and sometimes impossible to generate with conventional methods. Pedigrees ascertained with data from pre-existing genealogy databases and cancer registries can save effort and contain more information than traditional pedigrees. Genetic services should consider generating EGP’s which requires access to an accurate genealogy database and cancer registry. Local data protection laws and regulations have to be addressed.

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
Fig. 2

Similar content being viewed by others

References

  1. NCCN Guidelines Version 2.2016 BRCA-Related Breast and/or Ovarian Cancer Syndrome (2016) National Comprehensive Cancer Network. http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed 27 March 2016

  2. Moller P, Hagen AI, Apold J, Maehle L, Clark N, Fiane B, Lovslett K, Hovig E, Vabo A (2007) Genetic epidemiology of BRCA mutations–family history detects less than 50% of the mutation carriers. Eur J Cancer 43(11):1713–1717. https://doi.org/10.1016/j.ejca.2007.04.023

    Article  CAS  PubMed  Google Scholar 

  3. Solomon BL, Whitman T, Wood ME (2016) Contribution of extended family history in assessment of risk for breast and colon cancer. BMC Fam Pract 17(1):126. https://doi.org/10.1186/s12875-016-0521-0

    Article  PubMed  PubMed Central  Google Scholar 

  4. Augustinsson A, Ellberg C, Kristoffersson U, Borg A, Olsson H (2017) Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer. Acta Oncol 57:595–603. https://doi.org/10.1080/0284186X.2017.1404635

    Article  PubMed  Google Scholar 

  5. Augustinsson A, Ellberg C, Kristoffersson U, Borg A, Olsson H (2018) Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer. Acta Oncol 57(5):595–603. https://doi.org/10.1080/0284186X.2017.1404635

    Article  PubMed  Google Scholar 

  6. Weitzel JN, Lagos VI, Cullinane CA, Gambol PJ, Culver JO, Blazer KR, Palomares MR, Lowstuter KJ, MacDonald DJ (2007) Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA 297(23):2587–2595. https://doi.org/10.1001/jama.297.23.2587

    Article  CAS  PubMed  Google Scholar 

  7. Forrest K, Simpson SA, Wilson BJ, van Teijlingen ER, McKee L, Haites N, Matthews E (2003) To tell or not to tell: barriers and facilitators in family communication about genetic risk. Clin Genet 64(4):317–326

    Article  CAS  PubMed  Google Scholar 

  8. Lim JN, Hewison J (2014) Do people really know what makes a family history of cancer? Health Expect 17(6):818–825. https://doi.org/10.1111/j.1369-7625.2012.00808.x

    Article  PubMed  Google Scholar 

  9. Kerber RA, Slattery ML (1997) Comparison of self-reported and database-linked family history of cancer data in a case-control study. Am J Epidemiol 146(3):244–248

    Article  CAS  PubMed  Google Scholar 

  10. Mitchell RJ, Brewster D, Campbell H, Porteous ME, Wyllie AH, Bird CC, Dunlop MG (2004) Accuracy of reporting of family history of colorectal cancer. Gut 53(2):291–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Roth FL, Camey SA, Caleffi M, Schuler-Faccini L, Palmero EI, Bochi C, Moreira SM, Kalakun L, Giugliani R, Ashton-Prolla P (2009) Consistency of self-reported first-degree family history of cancer in a population-based study. Fam Cancer 8(3):195–202. https://doi.org/10.1007/s10689-008-9228-2

    Article  PubMed  Google Scholar 

  12. van Dijk DA, Oostindier MJ, Kloosterman-Boele WM, Krijnen P, Vasen HF, Hereditary Tumor Study Group of the Comprehensive Cancer Centre W (2007) Family history is neglected in the work-up of patients with colorectal cancer: a quality assessment using cancer registry data. Fam Cancer 6(1):131–134. https://doi.org/10.1007/s10689-006-9114-8

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wood ME, Kadlubek P, Pham TH, Wollins DS, Lu KH, Weitzel JN, Neuss MN, Hughes KS (2014) Quality of cancer family history and referral for genetic counseling and testing among oncology practices: a pilot test of quality measures as part of the american society of clinical oncology quality oncology practice initiative. J Clin Oncol 32(8):824–829. https://doi.org/10.1200/Jco.2013.51.4661

    Article  PubMed  PubMed Central  Google Scholar 

  14. World Health Organization (2016) Breast cancer: prevention and control. http://www.who.int/cancer/detection/breastcancer/en/index1.html. Accessed 15 Aug 2016

  15. Engholm GFJ, Christensen N, Bray F, Gjerstorff ML, Klint Å (2016) NORDCAN

  16. Icelandic Cancer Society (2016) Icelandic Cancer Registry,. Icelandic Cancer Registry at Icelandic Cancer Society. http://www.cancerregistry.is. Accessed 10 Aug 2016

  17. Pukkala E, Engholm G, Højsgaard Schmidt LK, Storm H, Khan S, Lambe M, Pettersson D, Ólafsdóttir E, Tryggvadóttir L, Hakanen T, Malila N, Virtanen A, Johannesen TB, Larønningen S, Ursin G (2017) Nordic Cancer Registries—an overview of their procedures and data comparability. Acta Oncol 57:440–455. https://doi.org/10.1080/0284186X.2017.1407039

    Article  PubMed  Google Scholar 

  18. Balmana J, Diez O, Castiglione M, Group EGW (2009) BRCA in breast cancer: ESMO clinical recommendations. Ann Oncol 20(Suppl 4):19–20. https://doi.org/10.1093/annonc/mdp116

    Article  PubMed  Google Scholar 

  19. Gudbjartsson DF, Helgason H, Gudjonsson SA, Zink F, Oddson A, Gylfason A, Besenbacher S, Magnusson G, Halldorsson BV, Hjartarson E, Sigurdsson GT, Stacey SN, Frigge ML, Holm H, Saemundsdottir J, Helgadottir HT, Johannsdottir H, Sigfusson G, Thorgeirsson G, Sverrisson JT, Gretarsdottir S, Walters GB, Rafnar T, Thjodleifsson B, Bjornsson ES, Olafsson S, Thorarinsdottir H, Steingrimsdottir T, Gudmundsdottir TS, Theodors A, Jonasson JG, Sigurdsson A, Bjornsdottir G, Jonsson JJ, Thorarensen O, Ludvigsson P, Gudbjartsson H, Eyjolfsson GI, Sigurdardottir O, Olafsson I, Arnar DO, Magnusson OT, Kong A, Masson G, Thorsteinsdottir U, Helgason A, Sulem P, Stefansson K (2015) Large-scale whole-genome sequencing of the Icelandic population. Nat Genet 47(5):435–444. https://doi.org/10.1038/ng.3247

    Article  CAS  PubMed  Google Scholar 

  20. Thorlacius S, Sigurdsson S, Bjarnadottir H, Olafsdottir G, Jonasson JG, Tryggvadottir L, Tulinius H, Eyfjord JE (1997) Study of a single BRCA2 mutation with high carrier frequency in a small population. Am J Hum Genet 60(5):1079–1084

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Petrucelli N, Daly MB, Feldman GL (2010) Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med 12(5):245–259. https://doi.org/10.1097/GIM.0b013e3181d38f2f

    Article  CAS  PubMed  Google Scholar 

  22. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, Brca, Consortium BC, McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre L, Berthet P, Hooning MJ, van der Kolk LE, Kets CM, Adank MA, John EM, Chung WK, Andrulis IL, Southey M, Daly MB, Buys SS, Osorio A, Engel C, Kast K, Schmutzler RK, Caldes T, Jakubowska A, Simard J, Friedlander ML, McLachlan SA, Machackova E, Foretova L, Tan YY, Singer CF, Olah E, Gerdes AM, Arver B, Olsson H (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416. https://doi.org/10.1001/jama.2017.7112

    Article  CAS  PubMed  Google Scholar 

  23. Tryggvadottir L, Sigvaldason H, Olafsdottir GH, Jonasson JG, Jonsson T, Tulinius H, Eyfjord JE (2006) Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920–2000. J Natl Cancer Inst 98(2):116–122. https://doi.org/10.1093/jnci/djj012

    Article  CAS  PubMed  Google Scholar 

  24. Tulinius H (2011) Multigenerational information: the example of the Icelandic Genealogy Database. Methods Mol Biol 675:221–229. https://doi.org/10.1007/978-1-59745-423-0_11

    Article  CAS  PubMed  Google Scholar 

  25. Stefansdottir V, Arngrimsson R, Jonsson JJ (2013) Iceland-genetic counseling services. J Genet Couns 22(6):907–910. https://doi.org/10.1007/s10897-013-9640-0

    Article  PubMed  Google Scholar 

  26. Microsoft RANDBETWEEN function. Microsoft. https://support.office.com/en-us/article/RANDBETWEEN-function-4cc7f0d1-87dc-4eb7-987f-a469ab381685. Accessed 10 Aug 2016

  27. Sigurdardottir LG, Jonasson JG, Stefansdottir S, Jonsdottir A, Olafsdottir GH, Olafsdottir EJ, Tryggvadottir L (2012) Data quality at the Icelandic Cancer Registry: comparability, validity, timeliness and completeness. Acta Oncol 51(7):880–889. https://doi.org/10.3109/0284186X.2012.698751

    Article  PubMed  Google Scholar 

  28. Cannings C, Thompson EA, Skolnick MH (1978) Probability functions on complex pedigrees. Adv Appl Prob 10(1):26–61. https://doi.org/10.2307/1426718

    Article  Google Scholar 

  29. Elston RC, Stewart J (1971) A general model for the genetic analysis of pedigree data. Hum Hered 21(6):523–542. https://doi.org/10.1159/000152448

    Article  CAS  PubMed  Google Scholar 

  30. Stahlbom AK, Johansson H, Liljegren A, von Wachenfeldt A, Arver B (2012) Evaluation of the BOADICEA risk assessment model in women with a family history of breast cancer. Fam Cancer 11(1):33–40. https://doi.org/10.1007/s10689-011-9495-1

    Article  PubMed  Google Scholar 

  31. Lee AJ, Cunningham AP, Kuchenbaecker KB, Mavaddat N, Easton DF, Antoniou AC, Consortium of Investigators of Modifiers of B, Breast Cancer Association C (2014) BOADICEA breast cancer risk prediction model: updates to cancer incidences, tumour pathology and web interface. Br J Cancer 110(2):535–545. https://doi.org/10.1038/bjc.2013.730

    Article  CAS  PubMed  Google Scholar 

  32. Cyril Chapman (2016) Clinical Pedigree. CJC Pedigree Software Ltd. http://clinicalpedigree.com/index.html. Accessed 08 Aug 2016 2016

  33. MedCalc S (2016) ROC curve analysis in MedCalc. MedCalc Software. https://www.medcalc.org/manual/roc-curves.php

  34. Delong ER, Delong DM, Clarkepearson DI (1988) Comparing the areas under 2 or more correlated receiver operating characteristic curves—a nonparametric approach. Biometrics 44(3):837–845. https://doi.org/10.2307/2531595

    Article  CAS  PubMed  Google Scholar 

  35. Hanley JAMBT (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143(143):29–36

    Article  CAS  PubMed  Google Scholar 

  36. Snaedal G (1965) Cancer of the breast. a clinical study of treated and untreated patients in Iceland 1911–1955. Acta Chir Scand 90:1

    Google Scholar 

  37. Hemminki K, Czene K (2002) Attributable risks of familial cancer from the family-cancer database. Cancer Epidemiol Biomark Prev 11(12):1638–1644

    Google Scholar 

  38. Stefansdottir V, Johannsson OT, Skirton H, Tryggvadottir L, Tulinius H, Jonsson JJ (2013) The use of genealogy databases for risk assessment in genetic health service: a systematic review. J Community Genet 4(1):1–7. https://doi.org/10.1007/s12687-012-0103-3

    Article  PubMed  Google Scholar 

  39. Stefansdottir V, Johannsson OT, Skirton H, Jonsson JJ (2016) Counsellee’s experience of cancer genetic counselling with pedigrees that automatically incorporate genealogical and cancer database information. J Community Genet 7(3):229–235. https://doi.org/10.1007/s12687-016-0271-7

    Article  PubMed  PubMed Central  Google Scholar 

  40. Palsson G (2002) The life of family trees and the Book of Icelanders. Med Anthropol 21(3–4):337–367. https://doi.org/10.1080/01459740214078

    Article  PubMed  Google Scholar 

  41. Johnsson L, Helgesson G, Rafnar T, Halldorsdottir I, Chia KS, Eriksson S, Hansson MG (2010) Hypothetical and factual willingness to participate in biobank research. Eur J Hum Genet 18(11):1261–1264. https://doi.org/10.1038/ejhg.2010.106

    Article  PubMed  PubMed Central  Google Scholar 

  42. Royal College of Physicians RCoPaBSfHG (2011) Consent and confidentiality in clinical genetic practice: guidance on genetic testing and sharing genetic information,. 2nd edn., UK

  43. Bauer S (2014) From administrative infrastructure to biomedical resource: Danish population registries, the “Scandinavian laboratory,” and the “epidemiologist’s dream”. Sci Context 27(2):187–213

    Article  PubMed  Google Scholar 

  44. Trivedi B (2008) Biomedical science: betting the bank. Nature 452(7190):926–929. https://doi.org/10.1038/452926a

    Article  CAS  PubMed  Google Scholar 

  45. Wylie JE, Mineau GP (2003) Biomedical databases: protecting privacy and promoting research. Trends Biotechnol 21(3):113–116. https://doi.org/10.1016/S0167-7799(02)00039-2

    Article  CAS  PubMed  Google Scholar 

  46. Cannon Albright LA (2006) Computerized genealogies linked to medical histories for research and clinical care–a national view. In: AMIA Annual Symposium Proceedings, pp 1161–1162

  47. Cannon-Albright LA, Dintelman S, Maness T, Backus S, Thomas A, Meyer LJ (2013) Creation of a national resource with linked genealogy and phenotypic data: the Veterans Genealogy Project. Genet Med 15(7):541–547. https://doi.org/10.1038/gim.2012.171

    Article  PubMed  Google Scholar 

  48. Scottish/Northern Irish BBC (2003) BRCA1 and BRCA2 mutations in Scotland and Northern Ireland. Br J Cancer 88(8):1256–1262. https://doi.org/10.1038/sj.bjc.6600840

    Article  CAS  Google Scholar 

  49. Collyer S, De Mey R (1987) Public records and recognition of genetic disease in Scotland. Clin Genet 31(3):125–131

    Article  CAS  PubMed  Google Scholar 

  50. GLOBOCAN (2012) v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11, (2013) International Agency for Research on Cancer. http://globocan.iarc.fr. Accessed 26 Feb

  51. ANCR—Association of Nordic Cancer Registries (2016) Cancer registration in the Nordic countries. http://www.ancr.nu/cancer-data/. Accessed 10 July 2016

  52. Agarwala R, Biesecker LG, Schaffer AA (2003) Anabaptist genealogy database. Am J Med Genet C 121C(1):32–37. https://doi.org/10.1002/ajmg.c.20004

    Article  Google Scholar 

  53. Kaplanis J, Gordon A, Shor T, Weissbrod O, Geiger D, Wahl M, Gershovits M, Markus B, Sheikh M, Gymrek M, Bhatia G, MacArthur DG, Price AL, Erlich Y (2018) Quantitative analysis of population-scale family trees with millions of relatives. Science. https://doi.org/10.1126/science.aam9309

    Article  PubMed  PubMed Central  Google Scholar 

  54. Osatuyi B (2013) Information sharing on social media sites. Comput Hum Behav 29(6):2622–2631. https://doi.org/10.1016/j.chb.2013.07.001

    Article  Google Scholar 

  55. Jazwinski SM, Kim S, Dai J, Li L, Bi X, Jiang JC, Arnold J, Batzer MA, Walker JA, Welsh DA, Lefante CM, Volaufova J, Myers L, Su LJ, Hausman DB, Miceli MV, Ravussin E, Poon LW, Cherry KE, Welsch MA, Georgia Centenarian S, the Louisiana Healthy Aging S (2010) HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging. Aging Cell 9 (5):698–708. https://doi.org/10.1111/j.1474-9726.2010.00600.x

    Article  CAS  PubMed  Google Scholar 

  56. Doerr M, Teng K (2012) Family history: still relevant in the genomics era. Clev Clin J Med 79(5):331–336. https://doi.org/10.3949/ccjm.79a.11065

    Article  Google Scholar 

Download references

Acknowledgements

We thank Cyril Chapman for his help with Pedigree Assistant.

Author information

Authors and Affiliations

  1. Department of Genetics and Molecular Medicine, Landspitali – National University Hospital, Hringbraut, 101, Reykjavik, Iceland

    V. Stefansdottir, H. Olafsdottir & J. J. Jonsson

  2. Faculty of Health and Human Sciences, Plymouth University, Plymouth, UK

    H. Skirton

  3. Department Of Medical Oncology, Landspitali – National University Hospital, Reykjavik, Iceland

    O. Th. Johannsson

  4. Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland

    G. H. Olafsdottir & L. Tryggvadottir

  5. Department of Biochemistry and Molecular Biology, Univ. of Iceland, Reykjavik, Iceland

    V. Stefansdottir & J. J. Jonsson

  6. Faculty of Medicine, Univ. of Iceland, Reykjavik, Iceland

    L. Tryggvadottir

  7. Genetical Committee of the University of Iceland, Reykjavik, Iceland

    J. J. Jonsson

Authors
  1. V. Stefansdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Skirton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Th. Johannsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Olafsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. H. Olafsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Tryggvadottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. J. Jonsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. J. Jonsson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stefansdottir, V., Skirton, H., Johannsson, O.T. et al. Electronically ascertained extended pedigrees in breast cancer genetic counseling. Familial Cancer 18, 153–160 (2019). https://doi.org/10.1007/s10689-018-0105-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-018-0105-3

Keywords

Search

Navigation