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

A. C. Antoniou; 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-Culver; E. 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

doi:10.1038/sj.bjc.6604411

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

VTT Technical Research Centre of Finland

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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.

Original language	English
Pages (from-to)	1457-1466
Number of pages	10
Journal	British Journal of Cancer
Volume	98
Issue number	12
DOIs	https://doi.org/10.1038/sj.bjc.6604411
Publication status	Published - 17 Jun 2008
MoE publication type	Not Eligible

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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., ... 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

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title = "The BOADICEA model of genetic susceptibility to breast and ovarian cancers: Updates and extensions ",

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. ",

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

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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

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

SN - 0007-0920

VL - 98

SP - 1457

EP - 1466

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 12

ER -

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

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