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

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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 languageEnglish
Pages (from-to)98-107
JournalJournal of Medical Genetics
Issue number2
Publication statusPublished - Feb 2014

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