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Journal of Clinical Oncology, Vol 26, No 14 (May 10), 2008: pp. 2419 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.4335
CHEK2*1100delC Screening of Asian Women With a Family History of Breast Cancer Is UnwarrantedDivision of Medical Sciences, National Cancer Centre, Singapore and Department of Microbiology, National University of Singapore, Singapore
Department of Medical Oncology, National Cancer Centre, Singapore, and OncoCare Cancer Centre, Singapore To the Editor: We read with interest the article by Weisher et al1 in which the authors recommend genotyping for CHEK2*1100delC, in addition to BRCA1 and BRCA2 mutation screening, for women with a family history of breast cancer. In their report, only Northern or Eastern European ethnic groups and not other ethnic groups, were subjected to meta-analyses to determine breast cancer risks associated with this CHEK2 mutation.1 CHEK2*1100delC genotyping studies of Asian populations of Korean, Chinese, Japanese, South Indian, and Singaporean origin have so far not identified this mutation.2-6 Table 1 presents a summary of the Asian subjects that have been screened for the CHEK2*1100delC mutation.
None of our 94 Singaporean subjects of Asian descent who underwent genetic testing for BRCA1 and BRCA2 mutations utilizing a comprehensive strategy had the CHEK2*1100delC mutation. Screening was done using the multiplex ligation-dependent probe amplification method (P045 BRCA2/CHEK2 kit; MRC-Holland, Amsterdam, the Netherlands).5 All of these women had either a family history of breast or ovarian cancer or early-onset breast cancer, and were predominantly of Chinese, Malay, and Indian ethnicities.5 Therefore, based on the reasons outlined above and the points mentioned by Offit and Garber7 pertaining to population heterogeneity, cancer spectrum, variable penetrance, and the occurrence of phenocopies, we believe that genetic testing for CHEK2*1100delC in Asian women with a family history of breast cancer is not warranted. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS Supported by the SingHealth Cluster Research Grant No. EX020/2001 and National Medical Research Council (NMRC) of Singapore Grants No. NMRC/0711/2002 and NMRC/0763/2003. REFERENCES
1. Weischer M, Bojesen SE, Ellervik C, et al: CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: Meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol 26:542-548, 2008 2. Choi DH, Cho DY, Lee MH, 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 [epub ahead of print on January 3, 2008] 3. Song CG, Hu Z, Yuan WT, et al: CHEK2 c. 1100delC may not contribute to genetic background of hereditary breast cancer from Shanghai of China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 23:443-445, 2006[Medline] 4. Bell DW, Kim SH, Godwin AK, et al: Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts. Int J Cancer 121:2661-2667, 2007[CrossRef][Medline] 5. Ang P, Lim IHK, Lee TC, et al: BRCA1 and BRCA2 mutations in an Asian clinic-based population detected using a comprehensive detection strategy. Cancer Epidemiol Biomarkers Prev 16:2276-2284, 2007 6. Rajkumar T, Soumittra N, Nancy NK, et al: BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prev 4:203-208, 2003[Medline] 7. Offit K, Garber JE: Time to check CHEK2 in families with breast cancer? J Clin Oncol 26:519-520, 2008 Related Reply
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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