Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations

Richard M. Brohet; Maria E. Velthuizen; Frans B. L. Hogervorst; Hanne E. J. Meijers-Heijboer; Caroline Seynaeve; Margriet J. Collee; Senno Verhoef; Margreet G. E. M. Ausems; Nicoline Hoogerbrugge; Christi J. van Asperen; Encarna Gomez Garcia; Fred Menko; Jan C. Oosterwijk; Peter Devilee; Laura J. van't Veer; Flora E. van Leeuwen; Douglas F. Easton; Matti A. Rookus; Antonis C. Antoniou; H.  Resource

doi:10.1136/jmedgenet-2013-101974

Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations

Richard M. Brohet, Maria E. Velthuizen, Frans B. L. Hogervorst, Hanne E. J. Meijers-Heijboer, Caroline Seynaeve, Margriet J. Collee, Senno Verhoef, Margreet G. E. M. Ausems, Nicoline Hoogerbrugge, Christi J. van Asperen, Encarna Gomez Garcia, Fred Menko, Jan C. Oosterwijk, Peter Devilee, Laura J. van't Veer, Flora E. van Leeuwen, Douglas F. Easton, Matti A. Rookus^*, Antonis C. Antoniou, H. Resource

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. Results The average cumulative breast cancer risk by age 70years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (p(heterogeneity)=0.0006) and stronger family histories of breast cancer (p(heterogeneity)

Original language	English
Pages (from-to)	98-107
Journal	Journal of Medical Genetics
Volume	51
Issue number	2
DOIs	https://doi.org/10.1136/jmedgenet-2013-101974
Publication status	Published - Feb 2014

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10.1136/jmedgenet-2013-101974

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Brohet, R. M., Velthuizen, M. E., Hogervorst, F. B. L., Meijers-Heijboer, H. E. J., Seynaeve, C., Collee, M. J., Verhoef, S., Ausems, M. G. E. M., Hoogerbrugge, N., van Asperen, C. J., Garcia, E. G., Menko, F., Oosterwijk, J. C., Devilee, P., van't Veer, L. J., van Leeuwen, F. E., Easton, D. F., Rookus, M. A., Antoniou, A. C., & Resource , H. (2014). Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. Journal of Medical Genetics, 51(2), 98-107. https://doi.org/10.1136/jmedgenet-2013-101974

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title = "Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations",

abstract = "Background BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. Results The average cumulative breast cancer risk by age 70years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (p(heterogeneity)=0.0006) and stronger family histories of breast cancer (p(heterogeneity)",

author = "Brohet, {Richard M.} and Velthuizen, {Maria E.} and Hogervorst, {Frans B. L.} and Meijers-Heijboer, {Hanne E. J.} and Caroline Seynaeve and Collee, {Margriet J.} and Senno Verhoef and Ausems, {Margreet G. E. M.} and Nicoline Hoogerbrugge and {van Asperen}, {Christi J.} and Garcia, {Encarna Gomez} and Fred Menko and Oosterwijk, {Jan C.} and Peter Devilee and {van't Veer}, {Laura J.} and {van Leeuwen}, {Flora E.} and Easton, {Douglas F.} and Rookus, {Matti A.} and Antoniou, {Antonis C.} and H. Resource",

year = "2014",

month = feb,

doi = "10.1136/jmedgenet-2013-101974",

language = "English",

volume = "51",

pages = "98--107",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

publisher = "BMJ Publishing Group",

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Brohet, RM, Velthuizen, ME, Hogervorst, FBL, Meijers-Heijboer, HEJ, Seynaeve, C, Collee, MJ, Verhoef, S, Ausems, MGEM, Hoogerbrugge, N, van Asperen, CJ, Garcia, EG, Menko, F, Oosterwijk, JC, Devilee, P, van't Veer, LJ, van Leeuwen, FE, Easton, DF, Rookus, MA, Antoniou, AC & Resource , H 2014, 'Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations', Journal of Medical Genetics, vol. 51, no. 2, pp. 98-107. https://doi.org/10.1136/jmedgenet-2013-101974

Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. / Brohet, Richard M.; Velthuizen, Maria E.; Hogervorst, Frans B. L. et al.

In: Journal of Medical Genetics, Vol. 51, No. 2, 02.2014, p. 98-107.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations

AU - Brohet, Richard M.

AU - Velthuizen, Maria E.

AU - Hogervorst, Frans B. L.

AU - Meijers-Heijboer, Hanne E. J.

AU - Seynaeve, Caroline

AU - Collee, Margriet J.

AU - Verhoef, Senno

AU - Ausems, Margreet G. E. M.

AU - Hoogerbrugge, Nicoline

AU - van Asperen, Christi J.

AU - Garcia, Encarna Gomez

AU - Menko, Fred

AU - Oosterwijk, Jan C.

AU - Devilee, Peter

AU - van't Veer, Laura J.

AU - van Leeuwen, Flora E.

AU - Easton, Douglas F.

AU - Rookus, Matti A.

AU - Antoniou, Antonis C.

AU - Resource , H.

PY - 2014/2

Y1 - 2014/2

N2 - Background BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. Results The average cumulative breast cancer risk by age 70years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (p(heterogeneity)=0.0006) and stronger family histories of breast cancer (p(heterogeneity)

AB - Background BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. Results The average cumulative breast cancer risk by age 70years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (p(heterogeneity)=0.0006) and stronger family histories of breast cancer (p(heterogeneity)

U2 - 10.1136/jmedgenet-2013-101974

DO - 10.1136/jmedgenet-2013-101974

M3 - Article

VL - 51

SP - 98

EP - 107

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 2

ER -