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

A. C. Antoniou (Corresponding Author), A. P. Cunningham, J. Peto, D. G. Evans, F. Lalloo, S. A. Narod, H. A. Risch, J. E. Eyfjord, J. L. Hopper, M. C. Southey, H. Olsson, O. Johannsson, A. Borg, B. Pasini, P. Radice, S. Manoukian, D. M. Eccles, N. Tang, E. Olah, H. Anton-CulverE. Warner, J. Lubinski, J. Gronwald, B. Gorski, L. Tryggvadottir, K. Syrjakoski, O. P. Kallioniemi, H. Eerola, H. Nevanlinna, P. D.P. Pharoah, D. F. Easton

Research output: Contribution to journalArticleScientificpeer-review

10 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1457-1466
Number of pages10
JournalBritish Journal of Cancer
Volume98
Issue number12
DOIs
Publication statusPublished - 17 Jun 2008
MoE publication typeNot Eligible

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Genetic Predisposition to Disease
Ovarian Neoplasms
Breast Neoplasms
Neoplasms
Parturition
Male Breast Neoplasms
Gene Components
Cohort Effect
Genetic Loci
Incidence
Pancreatic Neoplasms
Population
Prostatic Neoplasms
Mutation

Cite this

Antoniou, A. C., Cunningham, A. P., Peto, J., Evans, D. G., Lalloo, F., Narod, S. A., ... Easton, D. F. (2008). The BOADICEA model of genetic susceptibility to breast and ovarian cancers: Updates and extensions . British Journal of Cancer, 98(12), 1457-1466. https://doi.org/10.1038/sj.bjc.6604411
Antoniou, A. C. ; 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. ; 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. / The BOADICEA model of genetic susceptibility to breast and ovarian cancers : Updates and extensions . In: British Journal of Cancer. 2008 ; Vol. 98, No. 12. pp. 1457-1466.
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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.",
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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, 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, PDP & Easton, DF 2008, 'The BOADICEA model of genetic susceptibility to breast and ovarian cancers: Updates and extensions ', British Journal of Cancer, vol. 98, no. 12, pp. 1457-1466. https://doi.org/10.1038/sj.bjc.6604411

The BOADICEA model of genetic susceptibility to breast and ovarian cancers : Updates and extensions . / Antoniou, A. C. (Corresponding Author); 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.; 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.

In: British Journal of Cancer, Vol. 98, No. 12, 17.06.2008, p. 1457-1466.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The BOADICEA model of genetic susceptibility to breast and ovarian cancers

T2 - Updates and extensions

AU - Antoniou, A. C.

AU - Cunningham, A. P.

AU - Peto, J.

AU - Evans, D. G.

AU - Lalloo, F.

AU - Narod, S. A.

AU - Risch, H. A.

AU - Eyfjord, J. E.

AU - Hopper, J. L.

AU - Southey, M. C.

AU - Olsson, H.

AU - Johannsson, O.

AU - Borg, A.

AU - Pasini, B.

AU - Radice, P.

AU - Manoukian, S.

AU - Eccles, D. M.

AU - Tang, N.

AU - Olah, E.

AU - Anton-Culver, H.

AU - Warner, E.

AU - Lubinski, J.

AU - Gronwald, J.

AU - Gorski, B.

AU - Tryggvadottir, L.

AU - Syrjakoski, K.

AU - Kallioniemi, O. P.

AU - Eerola, H.

AU - Nevanlinna, H.

AU - Pharoah, P. D.P.

AU - Easton, D. F.

PY - 2008/6/17

Y1 - 2008/6/17

N2 - 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.

AB - 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.

U2 - 10.1038/sj.bjc.6604411

DO - 10.1038/sj.bjc.6604411

M3 - Article

AN - SCOPUS:44949199138

VL - 98

SP - 1457

EP - 1466

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 12

ER -