AIM: The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. PATIENTS AND METHODS: Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2∗1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2∗1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n=2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2∗1100delC status of relatives was unknown. RESULTS: Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4-2.7), p<0.001) was observed in sisters of CHEK2∗1100delC positive index cases compared to sisters of CHEK2∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0-2.4) for mothers of CHEK2 positive versus negative index cases (p=0.041). For second primary breast cancers HR was increased in CHEK2∗1100delC positive index cases (HR 2.1, 95% CI: 1.3-3.3, p=0.003) and their sisters (HR 2.6, 95% CI: 1.1-6.1, p=0.025). CONCLUSION: There is an excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive non-BRCA1/2 familial breast cancer patients compared to non-CHEK2∗1100delC familial breast cancer relatives. Genotyping for the CHEK2∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs.
AIM: The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. PATIENTS AND METHODS: Cancer incidences were compared between first degree relatives of 107 familial breast cancerpatients positive for the CHEK2∗1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancerpatients without the CHEK2∗1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n=2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2∗1100delC status of relatives was unknown. RESULTS: Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4-2.7), p<0.001) was observed in sisters of CHEK2∗1100delC positive index cases compared to sisters of CHEK2∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0-2.4) for mothers of CHEK2 positive versus negative index cases (p=0.041). For second primary breast cancers HR was increased in CHEK2∗1100delC positive index cases (HR 2.1, 95% CI: 1.3-3.3, p=0.003) and their sisters (HR 2.6, 95% CI: 1.1-6.1, p=0.025). CONCLUSION: There is an excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive non-BRCA1/2 familial breast cancerpatients compared to non-CHEK2∗1100delCfamilial breast cancer relatives. Genotyping for the CHEK2∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs.
Authors: Taru A Muranen; Dario Greco; Carl Blomqvist; Kristiina Aittomäki; Sofia Khan; Frans Hogervorst; Senno Verhoef; Paul D P Pharoah; Alison M Dunning; Mitul Shah; Robert Luben; Stig E Bojesen; Børge G Nordestgaard; Minouk Schoemaker; Anthony Swerdlow; Montserrat García-Closas; Jonine Figueroa; Thilo Dörk; Natalia V Bogdanova; Per Hall; Jingmei Li; Elza Khusnutdinova; Marina Bermisheva; Vessela Kristensen; Anne-Lise Borresen-Dale; Julian Peto; Isabel Dos Santos Silva; Fergus J Couch; Janet E Olson; Peter Hillemans; Tjoung-Won Park-Simon; Hiltrud Brauch; Ute Hamann; Barbara Burwinkel; Frederik Marme; Alfons Meindl; Rita K Schmutzler; Angela Cox; Simon S Cross; Elinor J Sawyer; Ian Tomlinson; Diether Lambrechts; Matthieu Moisse; Annika Lindblom; Sara Margolin; Antoinette Hollestelle; John W M Martens; Peter A Fasching; Matthias W Beckmann; Irene L Andrulis; Julia A Knight; Hoda Anton-Culver; Argyrios Ziogas; Graham G Giles; Roger L Milne; Hermann Brenner; Volker Arndt; Arto Mannermaa; Veli-Matti Kosma; Jenny Chang-Claude; Anja Rudolph; Peter Devilee; Caroline Seynaeve; John L Hopper; Melissa C Southey; Esther M John; Alice S Whittemore; Manjeet K Bolla; Qin Wang; Kyriaki Michailidou; Joe Dennis; Douglas F Easton; Marjanka K Schmidt; Heli Nevanlinna Journal: Genet Med Date: 2016-10-06 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
Authors: Franziska Severin; Pascal Borry; Martina C Cornel; Norman Daniels; Florence Fellmann; Shirley Victoria Hodgson; Heidi C Howard; Jürgen John; Helena Kääriäinen; Hülya Kayserili; Alastair Kent; Florian Koerber; Ulf Kristoffersson; Mark Kroese; Celine Lewis; Georg Marckmann; Peter Meyer; Arne Pfeufer; Jörg Schmidtke; Heather Skirton; Lisbeth Tranebjærg; Wolf H Rogowski Journal: Eur J Hum Genet Date: 2014-09-24 Impact factor: 4.246