Journal List > J Breast Cancer > v.11(1) > 1036117

Choi, Cho, Lee, Park, and Haffty: Frequency of the CHEK2 1100delC Mutation in Korean Women with Early Onset Breast Cancer

Abstract

Purpose

Sequence variants in the cell cycle checkpoint kinase 2 (CHEK2 1100delC) are associated with an increased risk for breast cancer in women carrying this mutation. It is a low-penetrance breast cancer susceptibility allele, frequently observed in patients with a family history of breast cancer and/or young age, with the frequency varying 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 material from 101 Korean women patients with early-onset breast cancer.

Methods

One hundred and one Korean patients with early-onset breast cancer (40 yr old or younger) were selected for this study. All the patients had been screened for BRCA1 and BRCA2 mutations and 14 patients had deleterious mutations. Of the 101 patients entered for this study, 14 had family history of breast cancer and 7 had bilateral breast cancers. Mutation detection of CHEK2 1100delC was based on analysis of primer extension products generated from previously-amplified genomic DNA using a chip based MALDI-TOP mass spectrometry platform (Sequenom, Inc., San Diego, CA, USA).

Results

None of the 101 Korean patients with a family history of breast cancer and early-onset breast cancer who were candidates for the BRCA1 and BRCA2 test carried the 1100 delC mutation, which is observed in Caucasians with limited frequency.

Conclusion

We previously observed higher or comparable prevalence of BRCA1 and BRCA2 mutations in Korean patients with breast cancer compared to Caucasians. However, the CHEK2 1100delC mutation is absent or infrequent in Korean patients with breast cancer who have a high risk of BRCA1 and BRCA2 mutations, making its screening irrelevant.

Figures and Tables

Fig 1
MALDI-TOP MS CHEK2 mutation analysis flow chart.
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Fig 2
Example of MALDI-TOP CHEK2 mutation (wild type).
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Table 1
Clinicopathologic characteristics of patients (n=101)
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*s9 patients had both deleterious mutations and variants of unknown significance.

References

1. Korean Central Cancer Registry. 2002 Annual report of the Korean Central Cancer Registry. 2003. Gwacheon: Ministry of Health and Walfare.
2. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003. 302:643–646.
crossref
3. Malone KE, Daling JR, Neal C, Suter NM, O'brien C, Cushing-Haugen K, et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer. 2000. 88:1393–1402.
crossref
4. Lynch ED, Ostermeyer EA, Lee MK, Arena JF, Ji H, Dann J, et al. Inherited mutations in PTEN are associated with breast cancer, Cowen disease, and juvenile polyposis. Am J Hum Genet. 1997. 61:1254–1260.
crossref
5. Rapakko K, Allinen M, Syrjakoski K, Vahteristo P, Huusko P, vahakangas K, et al. Gernline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites. Br J Cancer. 2001. 84:116–119.
crossref
6. Meijers-Heijboer H, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Eng J Med. 2001. 345:159–164.
crossref
7. Choi DH, Lee MH, Bale AE, Carter D, Haffty BG. Incidence of BRCA1 and BRCA2 mutations in young Korean breast patients. J Clin Oncol. 2004. 22:1638–1645.
8. Kang HC, Kim IJ, Park JH, Kwon HJ, Won YJ, Heo SC, et al. Germline mutations of BRCA1 and BRCA2 in Korean breast and/or ovarian cancer families. Hum Mutat. 2002. 20:235.
crossref
9. Ahn SH, Hwang UK, Kwak BS, Yoon HS, Ku BK, Kang HJ, et al. Prevalence of BRCA1 and BRCA2 mutations in Korean breast cancer patients. J Korean Med Sci. 2004. 19:269–274.
crossref
10. Antoniou AC, Pharoah PD, McMullan G, Day NE, Ponder BA, Easton D. Evidence for further breast cancer susceptibility genes in addition to BRCA1and BRCA2 in a population-based study. Genet Epidemiol. 2001. 21:1–18.
crossref
11. Meijers-Heijbor H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 and BRCA2 mutations. Nat Genet. 2002. 31:55–59.
crossref
12. Vahteristo P, Bartkova J, Eerola H, Syrjakoski K, Ojala S, Kilpivaara O, et al. A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet. 2002. 71:432–438.
crossref
13. Oldenburg RA, Kroeze-Jansema K, Kraan J, Morreau H, Klijn JG, Hoogerbrugge N, et al. The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple case families. Cancer Res. 2003. 63:8153–8157.
14. Offit K, Pierce H, Kirchhoff T, Kolachana P, Rapaport B, Gregersen P, et al. Frequence of CHEK2*1100delC in New York breast cancer cases and controls. BMC Med Genet. 2003. 4:1.
crossref
15. The 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.
16. Weischer M, Bojesen SE, Tybjoerg-Hansen A, Axelsson CK, Nordestgaard BG. Increased risk of breast cancer associated with CHEK2*1100delC. J Clin Oncol. 2007. 25:57–63.
crossref
17. Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, et al. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006. 295:1379–1388.
crossref
18. Rajkumar T, oumittra N, Nancy NK, Swaminathan R, Sridevi V, Shanta V. BRCA1, BRCA2 and CHEK2 (1100 delC) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prev. 2003. 4:203–208.
19. Cybulski C, Gorski B, Huzarski T, Byrski T, Gronwald J, Debniak T, et al. CHEK2-positive breast cancers in young Polish women. Clin Cancer Res. 2006. 12:4832–4835.
crossref
20. Schmidt MK, Tollenaar RA, de Kemp SR, Broeks A, Cornelisse CJ, Smit VT, et al. Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC Germline mutation. J Clin Oncol. 2007. 25:64–69.
crossref
21. Meyer A, Dork T, Sohn C, Karstens JH, Bremer M. Breast cancer in patients carrying a germ-line CHEK2 mutation: outcome after breast conserving surgery and adjuvant radiotherapy. Radiother Oncol. 2007. 82:349–353.
crossref
22. Syrjakoski K, Kuukasjarvi T, Auvinen A, Kallioniemi OP. CHEK2 1100delC is not a risk factor for male breast cancer population. Int J Cancer. 2004. 108:475–476.
crossref
23. Neuhausen S, Dunning A, Steele L, Yakumo K, Hoffman M, Szabo C, et al. Role of CHEK2*1100delC in unselected series of Non-BRCA1/2 male breast cancers. Int J Cancer. 204. 108:477–478.
crossref
24. Ohayon T, Gal I, Baruch RG, Szabo C, Friedman E. CHEK2*1100delC and male breast cancer risk in Israel. Int J Cancer. 2004. 108:479–480.
crossref
25. Bernstein JL, Teraoka SN, John EM, Andrulis IL, Knight JA, Lapinski R, et al. The CHEK2*1100delC allelic variant and risk of breast cancer: screening results from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2006. 15:348–352.
crossref
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