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Cancer risks in BRCA2 families: estimates for sites other than breast and ovary
  1. C J van Asperen1,*,
  2. R M Brohet12,*,
  3. E J Meijers-Heijboer2,
  4. N Hoogerbrugge3,
  5. S Verhoef4,
  6. H F A Vasen5,
  7. M G E M Ausems6,
  8. F H Menko7,
  9. E B Gomez Garcia8,
  10. J G M Klijn9,
  11. F B L Hogervorst4,
  12. J C van Houwelingen10,
  13. L J van’t Veer11,
  14. M A Rookus12,
  15. F E van Leeuwen12,
  16. on behalf of the Netherlands Collaborative Group on Hereditary Breast Cancer (HEBON)
  1. 1Center for Human and Clinical Genetics, Department of Clinical Genetics, Leiden University Medical Center
  2. 2Department of Clinical Genetics, Erasmus Medical Center, Rotterdam
  3. 3Department of Clinical Genetics, Nijmegen Medical Center, Nijmegen
  4. 4Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam
  5. 5The Netherlands Foundation for the detection of hereditary tumours, Leiden
  6. 6Department of Medical Genetics, University Medical Center Utrecht, Utrecht
  7. 7Department of Clinical Genetics and Human Genetics, VU University Medical Center, Amsterdam
  8. 8Department of Clinical Genetics, Maastricht University Medical Center, Maastricht
  9. 9Department of Medical Oncology, Erasmus Medical Center Daniel den Hoed, Rotterdam
  10. 10Department of Medical Statistics, Leiden University Medical Center, Leiden
  11. 11Department of Pathology, the Netherlands Cancer Institute, Amsterdam
  12. 12Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  1. Correspondence to:
 Professor Dr F E van Leeuwen
 Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;


Background: In BRCA2 mutation carriers, increased risks have been reported for several cancer sites besides breast and ovary. As most of the families included in earlier reports were selected on the basis of multiple breast/ovarian cancer cases, it is possible that risk estimates may differ in mutation carriers with a less striking family history.

Methods: In the Netherlands, 139 BRCA2 families with 66 different pathogenic mutations were included in a nationwide study. To avoid testing bias, we chose not to estimate risk in typed carriers, but rather in male and female family members with a 50% prior probability of being a carrier (n = 1811). The relative risk (RR) for each cancer site with the exception of breast and ovarian cancer was determined by comparing observed numbers with those expected, based on Dutch cancer incidence rates.

Results: We observed an excess risk for four cancer sites: pancreas (RR 5.9; 95% confidence interval (CI) 3.2 to 10.0), prostate (2.5; 1.6 to 3.8), bone (14.4; 2.9 to 42.1) and pharynx (7.3; 2.0 to 18.6). A small increase was observed for cancer of the digestive tract (1.5; 1.1 to 1.9). Histological verification was available for 46% of the tumours. Nearly all increased risks reached statistical significance for men only. Cancer risks tended to be higher for people before the age of 65 years. Moreover, families with mutations outside the previously defined ovarian cancer cluster region tended to have a higher cancer risk.

Conclusions: We found that BRCA2 carriers are at increased risk for cancers of the prostate and pancreas, and possibly bone and pharynx. Larger databases with extended follow up are needed to provide insight into mutation specific risks of selected carriers in BRCA2 families.

  • BRCA2
  • Cancer risk
  • breast cancer
  • other sites
  • ovarian cancer

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  • The first two authors contributed equally to this manuscript.

  • The Netherlands Collaborative Group on Hereditary Breast Cancer (HEBON) comprises: Netherlands Cancer Institute: E J Th Rutgers, F E van Leeuwen, L J van ’t Veer, F B L Hogervorst; VU Medical Center: F H Menko, J J P Gille, S Meijer, C J Dommering; Academic Medical Center: G van Tienhoven, I Kluyt, C W Taat (deceased) Groningen University Hospital: J C Oosterwijk, J de Vries, A H van der Hout; Erasmus Medical Center Daniel den Hoed: J G M Klijn, A N van Geel, C T M Brekelman, C M J C Seynaeve; Erasmus Medical Center Dept of Clinical Genetics: E J Meijers-Heijboer, A W M van den Ouweland; Leiden University Medical Center: R A E M Tollenaar, P Devilee, C J van Asperen, G R Vink; University Medical Center Utrecht: M G E M Ausems, R v d Luijt, C Warlam-Rodenhuis; Nijmegen Medical Center: N Hoogerbrugge, L A V M Beex, M Ligtenberg; Maastricht Medical Center: P S G J Hupperets, M Von Meyenfeldt, E B Gomez-Garzia, A van den Wijngaard Netherlands Foundation for the Detection of Hereditary Tumours: H F A Vasen, I S J Van Leeuwen.

  • This work was financially supported by the Dutch Cancer Society (grant NKI 98–1854).

  • Competing interests: none declared