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CHEK2 *1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer–Specific Death, and Increased Risk of a Second Breast Cancer

2012; Lippincott Williams & Wilkins; Volume: 30; Issue: 35 Linguagem: Inglês

10.1200/jco.2012.42.7336

1527-7755

Maren Weischer, Børge G. Nordestgaard, Paul D.P. Pharoah, Manjeet K. Bolla, Heli Nevanlinna, Laura J. vanʼt Veer, Montserrat García‐Closas, John L. Hopper, Per Hall, Irene L. Andrulis, Peter Devilee, Peter A. Fasching, Hoda Anton‐Culver, Diether Lambrechts, Maartje J. Hooning, Angela Cox, Graham G. Giles, Barbara Burwinkel, Annika Lindblom, Fergus J. Couch, Graham J. Mann, Grethe Grenaker Alnæs, Esther M. John, Thilo Dörk, Henrik Flyger, Alison M. Dunning, Qin Wang, Taru Muranen, Richard van Hien, Jonine D. 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 Reed, Gianluca Severi, Frederik Marmé, Sara Margolin, Janet E. Olson, Veli‐Matti Kosma, Vessela N. Kristensen, Alexander Miron, Natalia Bogdanova, Mitul Shah, Carl Blomqvist, Annegien Broeks, Mark E. 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,

Genetic factors in colorectal cancer

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.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.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.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.