CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer–Specific Death, and Increased Risk of a Second Breast Cancer
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Published:2012-12-10
Issue:35
Volume:30
Page:4308-4316
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Weischer Maren1, Nordestgaard Børge G.1, Pharoah Paul1, Bolla Manjeet K.1, Nevanlinna Heli1, van't Veer Laura J.1, Garcia-Closas Montserrat1, Hopper John L.1, Hall Per1, Andrulis Irene L.1, Devilee Peter1, Fasching Peter A.1, Anton-Culver Hoda1, Lambrechts Diether1, Hooning Maartje1, Cox Angela1, Giles Graham G.1, Burwinkel Barbara1, Lindblom Annika1, Couch Fergus J.1, Mannermaa Arto1, Grenaker Alnæs Grethe1, John Esther M.1, Dörk Thilo1, Flyger Henrik1, Dunning Alison M.1, Wang Qin1, Muranen Taru A.1, van Hien Richard1, Figueroa Jonine1, Southey Melissa C.1, Czene Kamila1, Knight Julia A.1, Tollenaar Rob A.E.M.1, Beckmann Matthias W.1, Ziogas Argyrios1, Christiaens Marie-Rose1, Collée Johanna Margriet1, Reed Malcolm W.R.1, Severi Gianluca1, Marme Frederik1, Margolin Sara1, Olson Janet E.1, Kosma Veli-Matti1, Kristensen Vessela N.1, Miron Alexander1, Bogdanova Natalia1, Shah Mitul1, Blomqvist Carl1, Broeks Annegien1, Sherman Mark1, Phillips Kelly-Anne1, Li Jingmei1, Liu Jianjun1, Glendon Gord1, Seynaeve Caroline1, Ekici Arif B.1, Leunen Karin1, Kriege Mieke1, Cross Simon S.1, Baglietto Laura1, Sohn Christof1, Wang Xianshu1, Kataja Vesa1, Børresen-Dale Anne-Lise1, Meyer Andreas1, Easton Douglas F.1, Schmidt Marjanka K.1, Bojesen Stig E.1
Affiliation:
1. Maren Weischer, Børge G. Nordestgaard, Henrik Flyger, and Stig E. Bojesen, University of Copenhagen, Copenhagen, Denmark; Paul Pharoah, Manjeet K. Bolla, Alison M. Dunning, Qin Wang, Mitul Shah, and Douglas F. Easton, University of Cambridge, Cambridge; Montserrat Garcia-Closas, Institute of Cancer Research, London; Angela Cox, Malcolm W.R. Reed, and Simon S. Cross, University of Sheffield, Sheffield, United Kingdom; Heli Nevanlinna, Taru A. Muranen, and Carl Blomqvist, University of Helsinki and...
Abstract
Purpose We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer–specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer–specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor–positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer–specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor–positive first breast cancer only. Conclusion Among women with estrogen receptor–positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer–specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
151 articles.
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