Breast Cancer Research and Treatment

, Volume 116, Issue 2, pp 397–400 | Cite as

CHEK2 1100delC and male breast cancer in the Netherlands

  • Marijke Wasielewski
  • Michael A. den Bakker
  • Ans van den Ouweland
  • Marion E. Meijer-van Gelder
  • Henk Portengen
  • Jan G. M. Klijn
  • Hanne Meijers-Heijboer
  • John A. Foekens
  • Mieke Schutte


Mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and CHEK2 are known risk factors for female breast cancer. Mutations in BRCA1 and BRCA2 also are associated with male breast cancer (MBC). Similarly, it had been suggested in the original CHEK2 identification report that the CHEK2 1100delC mutation confers an increased risk for MBC. Here, we have evaluated the risk of CHEK2 1100delC for MBC by genotyping CHEK2 1100delC in 23 familial and 71 unselected Dutch MBC cases. None of the 23 familial MBC cases carried the CHEK2 1100delC mutation. In contrast, CHEK2 1100delC was present in 3 of the 71 (4.2%) unselected MBC cases, which was significantly more prevalent than the 1.1% Dutch population frequency assessed in 1,692 individuals (P = 0.05, OR = 4.1, 95% CI 1.2–14.3). Our data suggest that, in the Netherlands, CHEK2 1100delC is associated with an increased risk for MBC.


Cancer susceptibility CHEK2 CHK2 Male breast cancer 



Funding was provided by the Dutch Cancer Society, grant DDHK 2003-2862, and the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NOW).


  1. 1.
    Weiss JR, Moysich KB, Swede H (2005) Epidemiology of male breast cancer. Cancer Epidemiol Biomarkers Prev 14:20–26. doi: 10.1158/1055-9965.EPI-05-0414 PubMedCrossRefGoogle Scholar
  2. 2.
    Fentiman IS, Fourquet A, Hortobagyi GN (2006) Male breast cancer. Lancet 367:595–604. doi: 10.1016/S0140-6736(06)68226-3 PubMedCrossRefGoogle Scholar
  3. 3.
    Nahleh Z, Girnius S (2006) Male breast cancer: a gender issue. Nat Clin Pract Oncol 3:428–437. doi: 10.1038/ncponc0564 PubMedCrossRefGoogle Scholar
  4. 4.
    Meijers-Heijboer H, van den Ouweland A, Klijn J et al (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31:55–59. doi: 10.1038/ng879 PubMedCrossRefGoogle Scholar
  5. 5.
    Vahteristo P, Bartkova J, Eerola H et al (2002) A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet 71:432–438. doi: 10.1086/341943 PubMedCrossRefGoogle Scholar
  6. 6.
    Consortium CBCC-C (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. doi: 10.1086/421251 CrossRefGoogle Scholar
  7. 7.
    Choi DH, Cho DY, Lee MH et al (2008) The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation. Breast Cancer Res Treat. doi: 10.1007/5105490079878z
  8. 8.
    Dufault MR, Betz B, Wappenschmidt B et al (2004) Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer 110:320–325. doi: 10.1002/ijc.20073 PubMedCrossRefGoogle Scholar
  9. 9.
    Evans DG, Bulman M, Young K et al (2007) BRCA1/2 mutation analysis in male breast cancer families from North West England. Fam Cancer 7:113–117. doi: 10.1007/s10689-007-9153-9 PubMedCrossRefGoogle Scholar
  10. 10.
    Falchetti M, Lupi R, Rizzolo P et al (2008) BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases. Breast Cancer Res Treat 110:161–167. doi: 10.1007/s10549-007-9689-2 PubMedCrossRefGoogle Scholar
  11. 11.
    Friedrichsen DM, Malone KE, Doody DR, Daling JR, Ostrander EA (2004) Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women. Breast Cancer Res 6:R629–R635. doi: 10.1186/bcr933 PubMedCrossRefGoogle Scholar
  12. 12.
    Jekimovs CR, Chen X, Arnold J et al (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. doi: 10.1038/sj.bjc.6602381 PubMedCrossRefGoogle Scholar
  13. 13.
    Karhu R, Laurila E, Kallioniemi A, Syrjakoski K (2006) Large genomic BRCA2 rearrangements and male breast cancer. Cancer Detect Prev 30:530–534. doi: 10.1016/j.cdp.2006.10.002 PubMedCrossRefGoogle Scholar
  14. 14.
    Neuhausen S, Dunning A, Steele L et al (2004) Role of CHEK2*1100delC in unselected series of non-BRCA1/2 male breast cancers. Int J Cancer 108:477–478. doi: 10.1002/ijc.11385 PubMedCrossRefGoogle Scholar
  15. 15.
    Offit K, Pierce H, Kirchhoff T et al (2003) Frequency of CHEK2*1100delC in New York breast cancer cases and controls. BMC Med Genet 4:1. doi: 10.1186/1471-2350-4-1 PubMedCrossRefGoogle Scholar
  16. 16.
    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. doi: 10.1002/ijc.11603 PubMedCrossRefGoogle Scholar
  17. 17.
    Sodha N, Wilson C, Bullock SL, Phillimore H, Houlston RS, Eeles RA (2004) Analysis of familial male breast cancer for germline mutations in CHEK2. Cancer Lett 215:187–189. doi: 10.1016/j.canlet.2004.07.002 PubMedCrossRefGoogle Scholar
  18. 18.
    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. doi: 10.1002/ijc.11384 PubMedCrossRefGoogle Scholar
  19. 19.
    Meijers-Heijboer H, Wijnen J, Vasen H et al (2003) The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet 72:1308–1314. doi: 10.1086/375121 PubMedCrossRefGoogle Scholar
  20. 20.
    Wasielewski M, Vasen H, Wijnen J et al (2008) CHEK2 1100delC is a susceptibility allele for HNPCC-related colorectal cancer. Clin Cancer Res 14:4989–4994. doi: 10.1158/1078-0432.CCR-08-0389 PubMedCrossRefGoogle Scholar
  21. 21.
    Meijer-van Gelder ME, Look MP, Bolt-de Vries J, Peters HA, Klijn JG, Foekens JA (2001) Clinical relevance of biologic factors in male breast cancer. Breast Cancer Res Treat 68:249–260. doi: 10.1023/A:1012221921416 PubMedCrossRefGoogle Scholar
  22. 22.
    Easton DF, Pooley KA, Dunning AM et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093. doi: 10.1038/nature05887 PubMedCrossRefGoogle Scholar
  23. 23.
    James JJ, Evans AJ, Pinder SE et al (2003) Bone metastases from breast carcinoma: histopathological–radiological correlations and prognostic features. Br J Cancer 89:660–665. doi: 10.1038/sj.bjc.6601198 PubMedCrossRefGoogle Scholar
  24. 24.
    Smid M, Wang Y, Klijn JG et al (2006) Genes associated with breast cancer metastatic to bone. J Clin Oncol 24:2261–2267. doi: 10.1200/JCO.2005.03.8802 PubMedCrossRefGoogle Scholar
  25. 25.
    Kilpivaara O, Laiho P, Aaltonen LA, Nevanlinna H (2003) CHEK2 1100delC and colorectal cancer. J Med Genet 40:e110. doi: 10.1136/jmg.40.10.e110 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Marijke Wasielewski
    • 1
  • Michael A. den Bakker
    • 2
  • Ans van den Ouweland
    • 3
  • Marion E. Meijer-van Gelder
    • 1
  • Henk Portengen
    • 1
  • Jan G. M. Klijn
    • 1
  • Hanne Meijers-Heijboer
    • 1
    • 3
  • John A. Foekens
    • 1
    • 4
  • Mieke Schutte
    • 1
  1. 1.Department of Medical OncologyJosephine Nefkens Institute, Erasmus University Medical CenterRotterdamThe Netherlands
  2. 2.Department of PathologyJosephine Nefkens Institute, Erasmus University Medical CenterRotterdamThe Netherlands
  3. 3.Department of Clinical GeneticsErasmus University Medical CenterRotterdamThe Netherlands
  4. 4.Department of Cancer Genomics CentreErasmus University Medical CenterRotterdamThe Netherlands

Personalised recommendations