Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma Young Tae Kim a, * , Eun Ji Nam a , Bo Sung Yoon a , Sang Wun Kim a , Sung Hoon Kim a , Jae Hoon Kim a , Hyun Ki Kim b , Ja Seong Koo a , Jae Wook Kim a a Division of Gynecolgic Oncology, Department of Obstetrics and Gynecology, Institute of Women’s Life Science, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, South Korea b Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea Received 23 April 2005 Available online 9 August 2005 Abstract Objectives. Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Korean women remains to be elucidated. In addition, genetic polymorphisms may affect not only cancer development but also cancer progression and, as a result, could influence cancer phenotypes. The purposes of this study were, first, to investigate the presence of BRCA1 and BRCA2 mutations in women with ovarian cancer who were unselected for family history and, second, to evaluate the relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. Methods. We studied 37 women who were diagnosed with epithelial ovarian cancer and treated at the Yonsei University Hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using a PCR-DHPLC-sequencing method. The relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features was examined. Results. Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer result in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) that led to premature termination. The patient had no family history of breast or ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. Conclusion. Our results were consistent with the hypothesis that BRCA1 and BRCA2 mutations have a limited role in sporadic ovarian carcinogenesis in the Korean population. Furthermore, polymorphisms of certain, selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer. D 2005 Elsevier Inc. All rights reserved. Keywords: BRCA1; BRCA2; Germline mutation; Ovarian carcinoma; Polymorphism Introduction Ovarian carcinoma is second only to cervical cancer as the most common malignancy of gynecologic origin, with respect to both incidence and mortality in South Korea [1]. According to the 1999 annual report of the Korean Ministry of Health and Welfare, approximately 1000 women are newly diagnosed annually with an invasive cancer of this type, suggesting its importance in public health [2]. Two high-penetrance breast–ovarian cancer susceptibil- ity genes have been identified: BRCA1, by Miki in 1994, and BRCA2, by Wooster in 1995 [3,4]. Women born with mutations in the BRCA1 or BRCA2 genes have a lifetime risk of ovarian cancer of 40 to 65% and 20%, respectively [5]. BRCA1 is located in chromosome 17q21. The BRCA1 gene is composed of 24 exons, with an mRNA that is 7.8 kb in length and 22 coding exons translating into a protein of 1863 amino acids. BRCA2 is located in the proximal area of the retinoblastoma (RB) gene on chromosome 13q12 – q13. It is composed of 27 exons translating into a protein of 3418 amino acids [4]. Germline mutations of BRCA1 and BRCA2 are thought to be responsible for the development 0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.06.058 * Corresponding author. Fax: +82 2 313 8357. E-mail address: ytkchoi@yumc.yonsei.ac.kr (Y.T. Kim). Gynecologic Oncology 99 (2005) 585 – 590 www.elsevier.com/locate/ygyno