Skip to main content

Frequency of the CHEK2 1100delC mutation among women with early-onset and bilateral breast cancer

We read with great interest the recent Breast Cancer Research paper by Desrichard and colleagues [1] reporting the association between CHEK2 mutations and non-BRCA hereditary breast cancer risk. This report summarized the results of different case-control studies to provide an overview of CHEK2 1100delC mutation and susceptibility to early-onset breast cancer (EOBC) and bilateral breast cancer (BBC). We believe there are significant issues to note regarding the authors' study.

To investigate the role of CHEK2 1100delC mutation in BBC susceptibility, Desrichard and colleagues performed a systematic review and pooled analysis based on five studies. Notably, another study that showed contradictory results indicating that the 1100delC mutation might not be a modifier in BBC [2] was not included in these analyses. Rashid and colleagues [3] have also shared their data, which failed to identify CHEK2 1100delC mutations among cases of BBC. Interestingly, the study by de Jong and colleagues [4] categorized individuals with BBC as unselected breast cancer cases. However, the BBC cases were included in the group of 192 patients identified with early-onset/familial breast cancer from an Irish study [5]. Hence, ongoing uncertainty exists and, in our opinion, the conclusion reached by Desrichard and colleagues may not be fully supported by the available data.

An additional issue is the association between CHEK2 mutations and EOBC risk. Using the same search strategy as that of Desrichard and colleagues, we located three relevant case-control studies in PubMed comprising a total of 3,742 EOBC cases and 8,405 controls [68], which were not included in the pooled analyses. Furthermore, we have combined all of the studies on European populations into a new pooled analysis. By using a fixed-effect model, significant associations were found to be associated with CHEK2 1100delC mutation in patients with EOBC (odds ratio 3.14, 95% confidence interval 1.86 to 5.28).

In conclusion, the association between CHEK2 1100delC mutation and BBC risk may be complex, and further studies will likely be needed to clarify the correlation of BBC and familial breast cancer characteristics. Similarly, further studies on EOBC-specific populations would be helpful for the purpose of better evaluating the association between CHEK2 1100delC mutation and EOBC risk.



bilateral breast cancer


early-onset breast cancer.


  1. Desrichard A, Bidet Y, Uhrhammer N, Bignon YJ: CHEK2 contribution to hereditary breast cancer in non-BRCA families. Breast Cancer Res. 2011, 13: R119-10.1186/bcr3062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dufault MR, Betz B, Wappenschmidt B, Hofmann W, Bandick K, Golla A, Pietschmann A, Nestle-Krämling C, Rhiem K, Hüttner C, von Lindern C, Dall P, Kiechle M, Untch M, Jonat W, Meindl A, Scherneck S, Niederacher D, Schmutzler RK, Arnold N: Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer. 2004, 110: 320-325. 10.1002/ijc.20073.

    Article  CAS  PubMed  Google Scholar 

  3. Rashid MU, Jakubowska A, Justenhoven C, Harth V, Pesch B, Baisch C, Pierl CB, Brüning T, Ko Y, Benner A, Wichmann HE, Brauch H, Hamann U; GENICA Network: German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer. Eur J Cancer. 2005, 41: 2896-2903. 10.1016/j.ejca.2005.04.049.

    Article  CAS  PubMed  Google Scholar 

  4. de Jong MM, Nolte IM, Te Meerman GJ, van der Graaf WT, Oosterom E, Bruinenberg M, Steege G, Oosterwijk JC, van der Hout AH, Boezen HM, Schaapveld M, Kleibeuker JH, de Vries EG: No increased susceptibility to breast cancer from combined CHEK2 1100delC genotype and the HLA class III region risk factors. Eur J Cancer. 2005, 41: 1819-1823. 10.1016/j.ejca.2005.04.035.

    Article  CAS  PubMed  Google Scholar 

  5. McInerney NM, Miller N, Rowan A, Colleran G, Barclay E, Curran C, Kerin MJ, Tomlinson IP, Sawyer E: Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort. Breast Cancer Res Treat. 2010, 121: 203-210. 10.1007/s10549-009-0540-9.

    Article  CAS  PubMed  Google Scholar 

  6. 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, Le Marchand L, Henderson BE, Altshuler D, Haber DA, Freedman ML: Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts. Int J Cancer. 2007, 121: 2661-2667. 10.1002/ijc.23026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chekmariova EV, Sokolenko AP, Buslov KG, Iyevleva AG, Ulibina YM, Rozanov ME, Mitiushkina NV, Togo AV, Matsko DE, Voskresenskiy DA, Chagunava OL, Devilee P, Cornelisse C, Semiglazov VF, Imyanitov EN: CHEK2 1100delC mutation is frequent among Russian breast cancer patients. Breast Cancer Res Treat. 2006, 100: 99-102. 10.1007/s10549-006-9227-7.

    Article  CAS  PubMed  Google Scholar 

  8. Cybulski C, Wokołorczyk D, Huzarski T, Byrski T, Gronwald J, Górski B, Debniak T, Masojć B, Jakubowska A, van de Wetering T, Narod SA, Lubiŕski J: A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland. Breast Cancer Res Treat. 2007, 102: 119-122. 10.1007/s10549-006-9320-y.

    Article  CAS  PubMed  Google Scholar 

Download references


We thank Ms Yanfang Guo (Institute of Bioinformatics, School of Basic Medical Science, Southern Medical University, Guangzhou, China) for scientific editing.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Dapeng Ding or Wenli Ma.

Additional information

Competing interests

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ding, D., Zhang, Y., He, X. et al. Frequency of the CHEK2 1100delC mutation among women with early-onset and bilateral breast cancer. Breast Cancer Res 14, 401 (2012).

Download citation

  • Published:

  • DOI: