Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. Issue 2 (27th November 2013)

• Record Type: Journal Article
• Authors: Brohet, Richard M; Velthuizen, Maria E; Hogervorst, Frans B L; EJ Meijers-Heijboer, Hanne; Seynaeve, Caroline; Collée, Margriet J; Verhoef, Senno; Ausems, Margreet G E M; Hoogerbrugge, Nicoline; van Asperen, Christi J; Gómez García, Encarna; Menko, Fred; Oosterwijk, Jan C; Devilee, Peter; Veer, Laura J van't; van Leeuwen, Flora E; Easton, Douglas F; Rookus, Matti A; Antoniou, Antonis C
• Other Names: Rookus MA author non-byline.; Brohet RM author non-byline.; Hogervorst FBL author non-byline.; van Leeuwen FE author non-byline.; Verhoef S author non-byline.; Schmidt MK author non-byline.; de Lange JL author non-byline.; Collée JM author non-byline.; van den Ouweland AMW author non-byline.; Hooning MJ author non-byline.; Seynaeve C author non-byline.; van Deurzen CHM author non-byline.; van Asperen CJ author non-byline.; Wijnen JT author non-byline.; Tollenaar RAEM author non-byline.; Devilee P author non-byline.; van Cronenburg TCTEF author non-byline.; Kets CM author non-byline.; Mensenkamp AR author non-byline.; Ausems MGEM author non-byline.; van der Luijt RB author non-byline.; Aalfs CM author non-byline.; van Os TAM author non-byline.; Gille JJP author non-byline.; Waisfisz Q author non-byline.; Meijers-Heijboer HEJ author non-byline.; Gómez-Garcia EB author non-byline.; Blok MJ author non-byline.; Oosterwijk JC author non-byline.; van der Hout AH author non-byline.; Mourits MJ author non-byline.; de Bock GH author non-byline.; Vasen HFA author non-byline.;
• Is Part Of: Journal of medical genetics. Volume 51:Issue 2(2014)
• Page Start: 98
• Page End: 107
• Publication Date: 2013-11-27
• Subjects: Cancer: Breast -- Clinical Genetics -- Genetic Epidemiology -- Oncology; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2013-101974
• Languages: English
• ISSNs: 1468-6244

Abstract

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 70 years 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 (pheterogeneity = 0.0006) and stronger family histories of breast cancer (pheterogeneity <0.001). For BRCA1, our data suggest a significant association between the location of the mutation and the ratio of breast to ovarian cancer (p<0.001). By contrast, in BRCA2 families, no evidence was found for risk heterogeneity by birth cohort, family history or mutation location. Conclusions: BRCA1 mutation carriers conferred lower overall breast and ovarian cancer risks than reported so far, while the estimates of BRCA2 mutations were among the lowest. The low estimates for BRCA1 might be due to older birth cohorts, a moderate family history, or founder mutations located within specific regions of the gene. These results are important for a more accurate counselling of BRCA1/2 mutation carriers.