CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer

Maren Weischer, Børge G. Nordestgaard, Paul Pharoah, Manjeet K. Bolla, Heli Nevanlinna, Laura J. Van't Veer, Montserrat Garcia-Closas, John L. Hopper, Per Hall, Irene L. Andrulis, Peter Devilee, Peter A. Fasching, Hoda Anton-Culver, Diether Lambrechts, Maartje Hooning, Angela Cox, Graham G. Giles, Barbara Burwinkel, Annika Lindblom, Fergus J. CouchArto Mannermaa, Grethe Grenaker Alnæs, Esther M. John, Thilo Dörk, Henrik Flyger, Alison M. Dunning, Qin Wang, Taru A. Muranen, Richard Van Hien, Jonine Figueroa, Melissa C. Southey, Kamila Czene, Julia A. Knight, Rob A.E.M. Tollenaar, Matthias W. Beckmann, Argyrios Ziogas, Marie Rose Christiaens, Johanna Margriet Collée, Malcolm W.R. Reed, Gianluca Severi, Frederik Marme, Sara Margolin, Janet E. Olson, Veli Matti Kosma, Vessela N. Kristensen, Alexander Miron, Natalia Bogdanova, Mitul Shah, Carl Blomqvist, Annegien Broeks, Mark Sherman, Kelly Anne Phillips, Jingmei Li, Jianjun Liu, Gord Glendon, Caroline Seynaeve, Arif B. Ekici, Karin Leunen, Mieke Kriege, Simon S. Cross, Laura Baglietto, Christof Sohn, Xianshu Wang, Vesa Kataja, Anne Lise Børresen-Dale, Andreas Meyer, Douglas F. Easton, Marjanka K. Schmidt, Stig E. Bojesen

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4308-4316
Number of pages9
JournalJournal of Clinical Oncology
Volume30
Issue number35
DOIs
StatePublished - Dec 10 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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