Objective: The suppressor gene CHEK2 encodes a cell cycle checkpoint kinase, involved in cell cycle regulation, apoptosis and response to DNA damage. The aim of this study was to analyze the differences between CHEK2 mutation carriers (CHEK2*1100delC/I157T) and noncarriers with respect to clinicopathological factors. Methods: We reviewed the medical records of 100 early breast cancer patients (46 mutation carriers and 54 noncarriers) who were treated with chemotherapy, hormonotherapy or trastuzumab. Results:CHEK2 mutation carriers were older (>65 years) than noncarriers (17 vs. 7%; p = 0.215). Twenty-five (54%) of them had a history of cancer in the family. Gastric cancer in the family history was detected in 11% of mutation carriers and in 2% of noncarriers (p = 0.092). There was a trend for more frequent lymph node metastases in patients without the mutation in comparison to mutation carriers (46 vs. 28%; p = 0.098). Luminal B type breast cancer was detected more often in carriers (39 vs. 20%; p = 0.048). Breast-conserving treatment was also conducted more often in mutation carriers (57 vs. 31%; p = 0.015). Histologic grades G1/G2 were detected more frequently in mutation carriers (82 vs. 70%; p = 0.212). Conclusion: Mutation carriers were characterized by older age, a history of gastric cancer in the family, locally advanced disease, lower histologic grade and luminal B type breast cancer.

Keywords:
Breast cancer, Clinicopathological factors, CHEK2 mutation
1.
Hale V, Weischer M, Park JY: CHEK2*1100delC mutation and risk of prostate cancer. Prostate Cancer 2014;2014:294575.
2.
Liu C, Wang Y, Wang QS, Wang YJ: The CHEK2 I157T variant and breast cancer susceptibility: a systematic review and meta-analysis. Asian Pac J Cancer Prev 2012;4:1355-1360.
3.
Ahn J, Urist M, Prives C: The Chk2 protein kinase. DNA Repair (Amst) 2004;3:1039-1047.
4.
Roeb W, Higgins J, King MC: Response to DNA damage of CHEK2 missense mutations in familial breast cancer. Hum Mol Genet 2012;15:2738-2744.
5.
Nevanlinna H, Bartek J: The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 2006;25:5912-5919.
6.
Friedrichsen DM, Malone KE, Doody DR, Daling JR, Ostrander EA: Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women. Breast Cancer Res 2004;6:R629-R635.
7.
Kilpivaara O, Bartkova J, Eerola H, Syrjäkoski K, Vahteristo P, Lukas J, Blomqvist C, Holli K, Heikkilä P, Sauter G, Kallioniemi OP, Bartek J, Nevanlinna H: Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. Int J Cancer 2005;113:575-580.
8.
Desrichard A, Bidet Y, Uhrhammer N, Bignon YJ: CHEK2 contribution to hereditary breast cancer in non-BRCA families. Breast Cancer Res 2011;13:R119.
9.
Adank MA, Verhoef S, Oldenburg RA, Schmidt MK, Hooning MJ, Martens JW, Broeks A, Rookus M, Waisfisz Q, Witte BI, Jonker MA, Meijers-Heijboer H: Excess breast cancer risk in first degree relatives of CHEK2*1100delC positive familiar breast cancer cases. Eur J Cancer 2013;8:1993-1999.
10.
Weischer M, Bojesen SE, Tybjaerg-Hansen A, Axelsson CK, Nordestgaard BG: Increased risk of breast cancer associated with CHEK2*1100delC. J Clin Oncol 2007;1:57-63.
11.
Weischer M, Bojesen SE, Ellervik C, Tybjaerg-Hansen A, Nordestgaard BG: CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol 2008;4:542-548.
12.
Weischer M, Nordestgaard BG, Pharoah P, et al: CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol 2012;10:4308-4316.
13.
Easton D, McGuffog L, Thompson D, et al; CHEK2 Breast Cancer Case-Control Consortium: CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 2004;74:1175-1182.
14.
Han FF, Guo CL, Liu LH: The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis. DNA Cell Biol 2013;32:329-335.
15.
Kilpivaara O, Vahteristo P, Falck J, Syrjäkoski K, Eerola H, Easton D, Bartkova J, Lukas J, Heikkilä P, Aittomäki K, Holli K, Blomqvist C, Kallioniemi OP, Bartek J, Nevanlinna H: CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer 2004;111:543-547.
16.
Cybulski C, Gorski B, Huzarski T, Masojć B, Mierzejewski M, Debniak T, Teodorczyk U, Byrski T, Gronwald J, Matyjasik J, Zlowocka E, Lenner M, Grabowska E, Nej K, Castaneda J, Medrek K, Szymańska A, Szymańska J, Kurzawski G, Suchy J, Oszurek O, Witek A, Narod SA, Lubiński J: CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 2004;75:1131-1135.
17.
Broeks A, de Witte L, Nooijen A, Huseinovic A, Klijn JG, van Leeuwen FE, Russell NS, van't Veer LJ: Excess risk for contralateral breast cancer in CHEK2*1100delC germline mutation carriers. Breast Cancer Res Treat 2004;83:91-93.
18.
Kriege M, Hollestelle A, Jager A, Huijts PE, Berns EM, Sieuwerts AM, Meijer-van Gelder ME, Collée JM, Devilee P, Hooning MJ, Martens JW, Seynaeve C: Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. Br J Cancer 2014;111:1004-1013.
19.
Mellemkjaer L, Dahl C, Olsen JH, Bertelsen L, Guldberg P, Christensen J, Børresen-Dale AL, Stovall M, Langholz B, Bernstein L, Lynch CF, Malone KE, Haile RW, Andersson M, Thomas DC, Concannon P, Capanu M, Boice JD Jr; WECARE Study Collaborative Group, Bernstein JL: Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE study. Br J Cancer 2008;98:728-733.
20.
de Bock GH, Mourits MJ, Schutte M, Krol-Warmerdam EM, Seynaeve C, Blom J, Breakelmans CT, Meijers-Heijboren H, van Asperen CJ, Cornelisse CJ, Devilee P, Tollenaar RA, Klijn JG: Association between the CHEK2*1100delC germ line mutation and estrogen receptor status. Int J Gynecol Cancer 2006;16:552-555.
21.
Domagala D, Wokolorczyk D, Cybulski C, Huzarski T, Lubinski J, Domagala W: Different CHEK2 germline mutations are associated with distinct immunophenotypic molecular subtypes of breast cancer. Breast Cancer Res Treat 2012;132:937-945.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.