1. ¹Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
2. ²Section of Epidemiology, Institute of Cancer Research, Sutton, UK
3. ³Section of Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
4. ⁴Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Manchester, UK
5. ⁵Centre for Research on Women's Health, University of Toronto, Toronto, Canada
6. ⁶Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA
7. ⁷Faculty of Medicine, University of Iceland, Reykjavík, Iceland
8. ⁸Icelandic Cancer Society, Reykjavík, Iceland
9. ⁹Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia
10. ¹⁰Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
11. ¹¹Department of Oncology, Lund University Hospital, Lund, Sweden
12. ¹²Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
13. ¹³IFOM Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
14. ¹⁴Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
15. ¹⁵Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
16. ¹⁶National Institute of Oncology, Budapest, Hungary
17. ¹⁷Epidemiology Division, Department of Medicine, University of California – Irvine, Irvine, CA, USA
18. ¹⁸International Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin, Poland
19. ¹⁹Laboratory of Cancer Genetics, Institute of Medical Technology, Tampere University Hospital, Tampere, Finland
20. ²⁰Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
21. ²¹Cancer Research UK, Human Cancer Genetics Group, Department of Oncology, University of Cambridge, Cambridge, UK

Correspondence: Dr AC Antoniou, Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK. E-mail: antonis@srl.cam.ac.uk

Received 30 November 2007; Revised 14 February 2008; Accepted 21 February 2008; Published online 18 March 2008.

Abstract

Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920–1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).