PURPOSE: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers. EXPERIMENTAL DESIGN: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared. RESULTS: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups. CONCLUSION: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.
PURPOSE: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers. EXPERIMENTAL DESIGN: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared. RESULTS: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups. CONCLUSION: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.
Authors: Jacek Gronwald; Tomasz Byrski; Tomasz Huzarski; Oleg Oszurek; Anna Janicka; Jolanta Szymanska-Pasternak; Bohdan Górski; Janusz Menkiszak; Izabella Rzepka-Górska; Jan Lubinski Journal: Hered Cancer Clin Pract Date: 2008-06-15 Impact factor: 2.857
Authors: Florence Le Calvez-Kelm; Fabienne Lesueur; Francesca Damiola; Maxime Vallée; Catherine Voegele; Davit Babikyan; Geoffroy Durand; Nathalie Forey; Sandrine McKay-Chopin; Nivonirina Robinot; Tù Nguyen-Dumont; Alun Thomas; Graham B Byrnes; John L Hopper; Melissa C Southey; Irene L Andrulis; Esther M John; Sean V Tavtigian Journal: Breast Cancer Res Date: 2011-01-18 Impact factor: 6.466
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