Skip to main content

Advertisement

SpringerLink
Log in

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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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 334:137–142

    Article  CAS  Google Scholar 

  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 279:915–921

    Article  PubMed  CAS  Google Scholar 

  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 91:943–949

    Article  PubMed  CAS  Google Scholar 

  4. Matsuoka S, Huang M, Elledge SJ (1998) Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893–1897

    Article  PubMed  CAS  Google Scholar 

  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 31:55–59

    Article  CAS  Google Scholar 

  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 71:432–438

    Article  PubMed  CAS  Google Scholar 

  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 74:1175–1182

    Article  Google Scholar 

  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 25:57–63

    Article  PubMed  CAS  Google Scholar 

  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 108:54–56

    Article  PubMed  CAS  Google Scholar 

  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 53:305–308

    PubMed  CAS  Google Scholar 

  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 92:784–790

    Article  PubMed  CAS  Google Scholar 

  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 4:1

    Article  PubMed  Google Scholar 

  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 22:1638–1645

    Article  PubMed  CAS  Google Scholar 

  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 19:269–274

    Article  PubMed  CAS  Google Scholar 

  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 245:90–95

    Article  PubMed  CAS  Google Scholar 

  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 72:1308–1314

    Article  PubMed  CAS  Google Scholar 

  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 63:8153–8157

    PubMed  CAS  Google Scholar 

  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 25:64–69

    Article  PubMed  CAS  Google Scholar 

  20. Margolin S, Eiberg H, Lindblom A, Bisgaard ML (2007) CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer. BMC Cancer 7:163

    Article  PubMed  CAS  Google Scholar 

  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 90:165–167

    Article  PubMed  CAS  Google Scholar 

  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 24:100–101

    Article  PubMed  CAS  Google Scholar 

  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 110:320–325

    Article  PubMed  CAS  Google Scholar 

  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 41:2896–2903

    Article  PubMed  CAS  Google Scholar 

  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 121:2661–2667

    Article  PubMed  CAS  Google Scholar 

  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

    Google Scholar 

  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 108:475–476

    Article  PubMed  CAS  Google Scholar 

  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 108:477–478

    Article  PubMed  CAS  Google Scholar 

  30. Ohayon T, Gal I, Baruch RG, Szabo C, Friedman E (2004) CHEK2*1100delC and male breast cancer risk in Israel. Int J Cancer 108:479–480

    Article  PubMed  CAS  Google Scholar 

  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 41:731–735

    Article  PubMed  CAS  Google Scholar 

  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 82:349–353

    Article  PubMed  CAS  Google Scholar 

  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 72:1023–1028

    Article  PubMed  CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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 66:8966–8970

    Article  PubMed  CAS  Google Scholar 

  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 111:543–547

    Article  PubMed  CAS  Google Scholar 

  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 116:263–266

    Article  PubMed  CAS  Google Scholar 

  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 12:4832–4835

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from Korean Breast Cancer Foundation 05-03. This study was presented at St. Gallen Oncology Conference (Primary Therapy of Early Breast Cancer 10th International Conference, 2007).

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, # 50 Ilwon-dong, Kangnam-gu, Seoul, 135-710, South Korea

    Doo Ho Choi

  2. LabGenomics Clinical Research Institute, LabGenomics, Seoul, South Korea

    Dae Yeon Cho

  3. Department of Surgery, Soonchunhyang University College of Medicine, Seoul, South Korea

    Min Hyuk Lee

  4. Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, South Korea

    Hee Sook Park

  5. Department of Surgery, College of Medicine, University of Ulsan and Asan Medical Center, Seoul, South Korea

    Sei Hyun Ahn & Byung Ho Son

  6. Department of Radiation Oncology, Robert Wood Johnson Medical School, Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Bruce G. Haffty

Authors
  1. Doo Ho Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dae Yeon Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Hyuk Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hee Sook Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sei Hyun Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Byung Ho Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bruce G. Haffty
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Doo Ho Choi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, D.H., Cho, D.Y., Lee, M.H. et al. The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation. Breast Cancer Res Treat 112, 569–573 (2008). https://doi.org/10.1007/s10549-007-9878-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9878-z

Keywords

Search

Navigation