Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2008

01-12-2008 | Epidemiology

The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation

Authors: Doo Ho Choi, Dae Yeon Cho, Min Hyuk Lee, Hee Sook Park, Sei Hyun Ahn, Byung Ho Son, Bruce G. Haffty

Published in: Breast Cancer Research and Treatment | Issue 3/2008

Login to get access

Abstract

The germline CHEK2 1100delC mutation is a low penetrance breast cancer susceptibility allele, frequently observed in patient with family history of breast cancer and/or young age and the frequency varied according to race or ethnicity. In this study, we evaluated the significance of CHEK2 1100delC in predisposition to breast cancer by assessing its frequency in a material of 493 Korean breast cancer patients who had been screened for BRCA1 and BRCA2 mutations (42 patients had deleterious mutation of BRCA1/2). Mutation detection of CHEK2 1100delC was based upon analysis of primer extension products generated for previously amplified genomic DNA using a chip based MALDI-TOP mass spectrometry platform. After overall measurement automatically, assays which had bad peaks were checked again manually. None of the 493 Korean patients with breast cancer who were candidate for BRCA1 and BRCA2 test carried the 1100delC mutation observed in Caucasians with limited frequency. In the previous studies, we observed higher or comparable prevalence of BRCA1 and BRCA2 mutations in Korean patients with breast cancer compared to Caucasian breast cancer population. In the present study, we evaluated the role of a CHEK2 1100delC as a susceptibility mutation of breast cancer in the Korean population. However, our results suggest that this mutation is absent or may be very infrequent in Korean patients with breast cancer who have high risk of BRCA1 and BRCA2 mutation, making its screening irrelevant from the practical point view.
Literature
1.
Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA (1996) BRCA1 mutations in a population-based sample of young women with breast cancer. N Eng J Med 334:137–142CrossRef
2.
Newman B, Mu H, Butler LM, Millikan RC, Moorman PG, King MC (1998) Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 279:915–921PubMedCrossRef
3.
Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evance C, Deacon J, Stratton MR (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91:943–949PubMedCrossRef
4.
Matsuoka S, Huang M, Elledge SJ (1998) Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893–1897PubMedCrossRef
5.
Meijers-Heijbor H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, van Veghel-Plandsoen M, Elstrodt F, van Duijn C, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton D, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Evans DG, Houlston R, Murday V, Norod S, Peretz T, Peto J, Phelan C, Zhang HX, Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson KL, Weber B, Rahman N, Stratton MR, CHEK2-Breast cancer Consortium (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 and BRCA2 mutations. Nat Genet 31:55–59CrossRef
6.
Vahteristo P, Bartkova J, Eerola H, Syrjakoski K, Ojala S, Kilpivaara O, Tamminen A, Kononen J, Aitomaki K, Heikkila P, Holli K, Blomqvist C, Bartek J, Kallioniemi OP, Nevanlinna H (2002) A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet 71:432–438PubMedCrossRef
7.
The CHEK2 Breast Cancer Case-Control Consortium (2004) 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 74:1175–1182CrossRef
8.
Weischer M, Bojesen SE, Tybjoerg-Hansen A, Axelsson CK, Nordestgaard BG (2007) Increased risk of breast cancer associated with CHEK2*1100delC. J Clin Oncol 25:57–63PubMedCrossRef
9.
Osorio A, Rodriguez-Lopez R, Diez O, de la Hoya M, Martinez JI, Vega A, Esteban-Cardenosa E, Alononso C, Caldes T, Benitez J (2004) The breast cancer low-penetrance allele 1100delC in the CHEK2 gene is not present in Spanish familial breast cancer. Int J Cancer 108:54–56PubMedCrossRef
10.
Kwiatkowska E, Skasko E, Niwinska A, Wojciechowska-Lacka A, Rachtan J, Molong L, Nowakowska D, Konopka B, Janice-Jankowska A, Paszko Z, Steffen J (2006) Low frequency of the CHEK2*1100delC mutation among breast cancer probands from three regions of Poland. Neoplasma 53:305–308PubMed
11.
Jekimovs CR, Chen X, Arnold J, Gatei M, Richard DJ, kConFab Investigators, Spurdle AB, Khanna KK, Chenevix-Trench G (2005) Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals. Br J Cancer 92:784–790PubMedCrossRef
12.
Offit K, Pierce H, Kirchhoff T, Kolachana P, Rapaport B, Gregersen P, Johnson H, Yossepowitch O, Huang H, Satagopan J, Robson M, Scheuer L, Nafa K, Ellis N (2003) Frequency of CHEK2*1100delC in New York breast cancer cases and controls. BMC Med Genet 4:1PubMedCrossRef
13.
Gonzalez-Hormazabal P, Casro VG, Blanco R, Gomez F, Peralta O, Waugh E, Bravo T, Reyes JM, Jara L (2007) Absence of CHEK2 1100delC mutation in familial breast cancer cases from a South American population. Breast Cancer Res Treat Sep 18 [Epub ahead of print]
14.
Choi DH, Lee MH, Bale AE, Carter D, Haffty BG (2004) Incidence of BRCA1 and BRCA2 mutation in young Korean breast cancer patients. J Clin Oncol 22:1638–1645PubMedCrossRef
15.
Ahn SH, Hwang UK, Kwak BS, Kang HJ, Kim JS, Ko BK, Ko CD, Yoon KS, Cho DY Kim JS, Son BH (2004) Prevalence of BRCA1 and BRCA2 mutations in Korean breast cancer patients. J Korean Med Sci 19:269–274PubMedCrossRef
16.
Ahn SH, Son BH, Yoon KS, Noh DY, Han W, Kim SW, Lee ES, Park HL, Hong YJ, Choi JJ, Moon SY, Kim MJ, Kim KH, Kwak BS, Cho DY (2007) BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett 245:90–95PubMedCrossRef
17.
Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, Hollestelle A, Elstrodt F, van den Bos R, de Snoo A, Fat GT, Brekelmans C, Jagmohan S, Franken P, Verkuijlen P, van den Ouweland A, Chapman P, Tops C, Moslein G, Burn J, Lynch H, Klijn J, Fodde R, Schutte M (2003) The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet 72:1308–1314PubMedCrossRef
18.
Oldenburg RA, Kroeze-Jansema K, Kraan J, Morreau H, Klijn JG, Hoogerbrugge N, Ligtenberg MJ, van Asperen CJ, Vasen HF, Meijers C, Meijers-Heijboer H, de Bock TH, Cornelisse CJ, Devilee P (2003) The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple case families. Cancer Res 63:8153–8157PubMed
19.
Schmidt MK, Tollenaar RA, de Kemp SR, Broeks A, Cornelisse CJ, Smit VT, Peterse JL, van Leeuwen PF, van’t Veer LJ (2007) Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC Germline mutation. J Clin Oncol 25:64–69PubMedCrossRef
20.
Margolin S, Eiberg H, Lindblom A, Bisgaard ML (2007) CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer. BMC Cancer 7:163PubMedCrossRef
21.
Kleibl Z, Novotny J, Bezdickova D, Malik R, Kleiblova P, Forestova L, Petruzelka L, Ilencikova D, Cinek P, Pohlreich P (2005) The CHEK2 c.1100delC germline mutation rarely contributes to breast cancer development in the Czech Republic. Breast Cancer Res Treat 90:165–167PubMedCrossRef
22.
Gutierrez-Enriquez S, Balmana J, Baiget M, Diez O (2007) Detection of the CHEK2 1100delC mutation by MLPA BRCA1/2 analysis: a worthwhile strategy for clinical applicability in 1100delC low-frequency populations? Breast Cancer Res Treat Apr 26 [Epub ahead of print]
23.
Caligo MA, Agata S, Aceto G, Crucianelli R, Manoukian S, Peissel B, Scaini MC, Sensi E, Veschi S, Cama A, Radice P, Viel A, D’Andrea E, Montagna M (2004) The CHEK2 c.1100delC mutation plays an irrelevant role in breast cancer predisposition in Italy. Hum Mutat 24:100–101PubMedCrossRef
24.
Dufault MR, Betz B, Wappenschmidt B, Hoffman W, Bandick K, Golla A, Pietschmann A, Nestre-Kramling, Rheim K, Huttner C, von Lindern C, Dall P, Kiechle M, Untch M, Jonat W, Meindl A, Scherneck S, Niederacher D, Schmutzler RK, Arnold N (2004) Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer 110:320–325PubMedCrossRef
25.
Rashid MU, Jakubowska A, Justenhoven C, Harth V, Pesch B, Baisch C, Pierl CB, Bruning T, Ko Y, Benner A (2005) Wichmann HE, Brauch H, Hamann U, German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer. Eur J Cancer 41:2896–2903PubMedCrossRef
26.
Bell DW, Kim SH, Godwin AK, Schiripo TA, Harris PL, Haserlat SM, Wahrer DC, Haiman CA, Daly MB, Niendorf KB, Smith MR, Sgroi DC, Garber JE, Olopade OI, Marchand LL, Henderson BE, Altshuler D, Haber DA, Freedman ML (2007) Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts. Int J Cancer 121:2661–2667PubMedCrossRef
27.
Johnson N, Fletcher O, Naceur-Lombardelli C, dos Santos Silva I, Ashworth A, Peto J (2005) Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study. Lancet 366:2554–2557
28.
Syrjakoski K, Kuukasjarvi T, Auvinen A, Kallioniemi OP (2004) CHEK2 1100delC is not a risk factor for male breast cancer population. Int J Cancer 108:475–476PubMedCrossRef
29.
Neuhausen S, Dunning A, Steele L, Yakumo K, Hoffman M, Szabo C, Tee L, Baines C, Pharoah P, Goldgar D, Easton D (2004) Role of CHEK2*1100delC in unselected series of non-BRCA1/2 male breast cancers. Int J Cancer 108:477–478PubMedCrossRef
30.
Ohayon T, Gal I, Baruch RG, Szabo C, Friedman E (2004) CHEK2*1100delC and male breast cancer risk in Israel. Int J Cancer 108:479–480PubMedCrossRef
31.
Falchetti M, Lupi R, Rizzolo P, Ceccarelli K, Zanna I, Calo V, Tommasi S, Masala G, Paradiso A, Gullino A, Giannini G, Russo A, Palli D, Ottini L (2007) BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases. Breast Cancer Res Treat Jul 28 [Epub ahead of print]
32.
de Bock GH, Schutte M, Krol-Warmerdam EM, Seynaeve C, Blom J, Brekelmans CT, Meijers-Heijboer H, van Asperen CJ, Cornelisse CJ, Devilee P, Tollenaart RA, Klijn JG (2004) Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant. J Med Genet 41:731–735PubMedCrossRef
33.
Meyer A, Dork T, Sohn C, Karstens JH, Bremer M (2007) Breast cancer in patients carrying a germ-line CHEK2 mutation: outcome after breast conserving surgery and adjuvant radiotherapy. Radiother Oncol 82:349–353PubMedCrossRef
34.
Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG, Eccles D, Meijers C, Lohman F, Klijn J, van den Ouweland A (2003) The Breast Cancer Linkage Consortium, Futreal PA, Nathanson KL, Weber BL, Easton DF, Stratton M, Rahman N. Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. Am J Hum Genet 72:1023–1028PubMedCrossRef
35.
Kuschel B, Auranen A, Gregory CS, Day NE, Easton DF, Ponder BA, Dunning AM, Pharoah PD (2003) Common polymorphisms in Checkpoint Kinase 2 are not associated with breast cancer risk. Cancer Epidem Biomar 12:809–812
36.
Sodha N, Mantoni TS, Tavtigian SV, Eeles R, Garret MD (2006) Rare germ line CHEK2 variants identified in breast cancer families encode proteins that show impaired activation. Cancer Res 66:8966–8970PubMedCrossRef
37.
Kilpivaara O, Vahteristo P, Falck J, Syrjakoski K, Earola H, Easton D, Bartkova J, Lukas J, Heikkila P, Aittomaki K, Holli K, Blomqvist C, Kallionniemi OP, Bartek J, Nevanlinna H (2004) CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer 111:543–547PubMedCrossRef
38.
Bogdanova N, Enssen-Dubrowinskaja N, Feshchenko S, Lazjuk GI, Rogov YI, Dammann O, Bremer M, Karstens JH, Sohn C, Dork T (2005) Association of two mutations in the CHEK2 gene with breast cancer. Int J Cancer 116:263–266PubMedCrossRef
39.
Cybulski C, Gorski B, Huzarski T, Byrski T, Gronwald J, Debniak T, Wokolorczyk D, Jakubowska A, Kowalska E, Oszurek O, Narod SA, Lubinski J (2006) CHEK2-positive breast cancers in young Polish women. Clin Cancer Res 12:4832–4835PubMedCrossRef
Metadata
Title
The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation
Authors
Doo Ho Choi
Dae Yeon Cho
Min Hyuk Lee
Hee Sook Park
Sei Hyun Ahn
Byung Ho Son
Bruce G. Haffty
Publication date
01-12-2008
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2008
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9878-z

Other articles of this Issue 3/2008

Breast Cancer Research and Treatment 3/2008 Go to the issue

Clinical Trial

A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses

Clinical Trial

The MSKCC nomogram for prediction the likelihood of non-sentinel node involvement in a German breast cancer population

Clinical Trial

Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases

Epidemiology

Early radiation exposures and BRCA1-associated breast cancer in young women from Poland

Clinical Trial

Paget’s disease of the breast: the experience of the European institute of oncology and review of the literature

Preclinical Study

Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits