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PMID: 18349832 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions.

British journal of cancer ·Vol. 98 ·No. 8 ·2008-04-22 ·Pages 1457-66

Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, Borg A, Pasini B, Passini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tryggvadottir L, Syrjakoski K, Kallioniemi OP, Eerola H, Nevanlinna H, Pharoah PD, Easton DF

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).

MeSH Terms
Adult Age Factors Aged Breast Neoplasms/etiology,genetics Female Genes, BRCA1 Genes, BRCA2 Genetic Carrier Screening Genetic Predisposition to Disease Humans Middle Aged Models, Genetic Mutation Neoplasms, Second Primary/etiology,genetics Ovarian Neoplasms/etiology,genetics
Authors & Affiliations
32 authors, click to expand affiliations / ORCID
Antoniou A C
Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [email protected]
Cunningham A P
Peto J
Evans D G
Lalloo F
Narod S A
Risch H A
Eyfjord J E
Hopper J L
Southey M C
Olsson H
Johannsson O
Borg A
Pasini B
Passini B
Radice P
Manoukian S
Eccles D M
Tang N
Olah E
Anton-Culver H
Warner E
Lubinski J
Gronwald J
Gorski B
Tryggvadottir L
Syrjakoski K
Kallioniemi O-P
Eerola H
Nevanlinna H
Pharoah P D P
Easton D F
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
DOI
10.1038/sj.bjc.6604305
Email
[email protected]
Published
2008-04-22
Epub
2008-00-18
Pages
1457-66
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2361716
Subset
IM
Grants
NCI NIH HHS · R01 CA063678 · United States
NCI NIH HHS · R01 CA 63682 · United States
NCI NIH HHS · R01 CA063682 · United States
NCI NIH HHS · R01 CA 63678 · United States
Cancer Research UK · 10118 · United Kingdom
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1038/sj.bjc.6604305 PMC Full Text View journal details
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