BACKGROUND: Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors. This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk. METHODS AND RESULTS: Homozygosity for the CHEK2*1100delC allele was identified in 8/2554 Dutch independent familial non-BRCA1/2 breast cancer cases. The genotype relative risk for breast cancer of homozygous and heterozygous familial breast cancer cases was 101.34 (95% CI 4.47 to 121 000) and 4.04 (95% CI 0.88 to 21.0), respectively. Female homozygotes appeared to have a greater than twofold increased breast cancer risk compared to familial CHEK2*1100delC heterozygotes (p=0.044). These results and the occurrence of multiple primary tumours in 7/10 homozygotes indicate a high cancer risk in homozygous women from non-BRCA1/2 families. CONCLUSIONS: Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non-BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2.
BACKGROUND: Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors. This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk. METHODS AND RESULTS: Homozygosity for the CHEK2*1100delC allele was identified in 8/2554 Dutch independent familial non-BRCA1/2 breast cancer cases. The genotype relative risk for breast cancer of homozygous and heterozygous familial breast cancer cases was 101.34 (95% CI 4.47 to 121 000) and 4.04 (95% CI 0.88 to 21.0), respectively. Female homozygotes appeared to have a greater than twofold increased breast cancer risk compared to familial CHEK2*1100delC heterozygotes (p=0.044). These results and the occurrence of multiple primary tumours in 7/10 homozygotes indicate a high cancer risk in homozygous women from non-BRCA1/2 families. CONCLUSIONS: Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non-BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2.
Authors: Petra E A Huijts; Antoinette Hollestelle; Brunilda Balliu; Jeanine J Houwing-Duistermaat; Caro M Meijers; Jannet C Blom; Bahar Ozturk; Elly M M Krol-Warmerdam; Juul Wijnen; Els M J J Berns; John W M Martens; Caroline Seynaeve; Lambertus A Kiemeney; Henricus F van der Heijden; Rob A E M Tollenaar; Peter Devilee; Christi J van Asperen Journal: Eur J Hum Genet Date: 2013-05-08 Impact factor: 4.246
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Authors: Irene Catucci; Ana Osorio; Brita Arver; Guido Neidhardt; Massimo Bogliolo; Federica Zanardi; Mirko Riboni; Simone Minardi; Roser Pujol; Jacopo Azzollini; Bernard Peissel; Siranoush Manoukian; Giovanna De Vecchi; Stefano Casola; Jan Hauke; Lisa Richters; Kerstin Rhiem; Rita K Schmutzler; Karin Wallander; Therese Törngren; Åke Borg; Paolo Radice; Jordi Surrallés; Eric Hahnen; Hans Ehrencrona; Anders Kvist; Javier Benitez; Paolo Peterlongo Journal: Genet Med Date: 2017-08-24 Impact factor: 8.822
Authors: Marjanka K Schmidt; Frans Hogervorst; Richard van Hien; Sten Cornelissen; Annegien Broeks; Muriel A Adank; Hanne Meijers; Quinten Waisfisz; Antoinette Hollestelle; Mieke Schutte; Ans van den Ouweland; Maartje Hooning; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Antonis C Antoniou; Volker Arndt; Marina Bermisheva; Natalia V Bogdanova; Manjeet K Bolla; Hiltrud Brauch; Hermann Brenner; Thomas Brüning; Barbara Burwinkel; Jenny Chang-Claude; Georgia Chenevix-Trench; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Alison M Dunning; Peter A Fasching; Jonine Figueroa; Olivia Fletcher; Henrik Flyger; Eva Galle; Montserrat García-Closas; Graham G Giles; Lothar Haeberle; Per Hall; Peter Hillemanns; John L Hopper; Anna Jakubowska; Esther M John; Michael Jones; Elza Khusnutdinova; Julia A Knight; Veli-Matti Kosma; Vessela Kristensen; Andrew Lee; Annika Lindblom; Jan Lubinski; Arto Mannermaa; Sara Margolin; Alfons Meindl; Roger L Milne; Taru A Muranen; Polly A Newcomb; Kenneth Offit; Tjoung-Won Park-Simon; Julian Peto; Paul D P Pharoah; Mark Robson; Anja Rudolph; Elinor J Sawyer; Rita K Schmutzler; Caroline Seynaeve; Julie Soens; Melissa C Southey; Amanda B Spurdle; Harald Surowy; Anthony Swerdlow; Rob A E M Tollenaar; Ian Tomlinson; Amy Trentham-Dietz; Celine Vachon; Qin Wang; Alice S Whittemore; Argyrios Ziogas; Lizet van der Kolk; Heli Nevanlinna; Thilo Dörk; Stig Bojesen; Douglas F Easton Journal: J Clin Oncol Date: 2016-06-06 Impact factor: 44.544