목적: 한국인에서 가족력과 무관하게 산발적으로 발생한 난소암 환자의 BRCA1 및 BRCA2의 배선 유전자 돌연변이를 확인하고 발생율을 구하여 이 자료를 향후 난소암 환자의 증상발현 전 진단에 활용할 수 있는지 조사하고 난소암 발생과 연관된 BRCA1 및 BRCA2 유전자의 다형성 (polymorphism)이 난소암 환자의 임상병리학적인 특징과 연관성이 있는지 살펴보고자 하였다. 연구 방법: 2002년 8월부터 2004년 3월까지 병기 결정을 위한 개복술을 시행 받고 병리학적으로 난소암을 확진 받았으며 가계도 분석에서 산발성 난소암으로 확인된 37명을 대상으로 말초 혈액을 채취하여 PCR-DHPLC-Sequencing method를 이용하여 BRCA1 및 BRCA2 유전자를 분석하였다. 결과: 1명의 난소암 환자에서 프레임 이동 (frame shift) 돌연변이가 발견되었다. 돌연변이는 BRCA1 유전자의 엑손 11K에 있는 코돈 1,218에서 3,746번째 염기에 adenine이 삽입 (insertion)되어 그 결과, 프레임이 이동하여 코돈 1,218에 정지 (stop) 코돈이 형성되어 절단 단백질 (truncated protein)을 생성하게 된다. 전체 환자 중 BRCA1 유전자 돌연변이율은 2.7%에 해당하였다. 37명의 난소암 환자의 BRCA2 유전자에서는 돌연변이가 발견되지 않았다. BRCA1 및 BRCA2 유전자형 분석 (genotyping)을 하는 중 얻어진 유전자다형성 중 rare allele frequency가 10% 이상인 다형성과 난소암의 임상병리학적인 특징과 비교하였으나 통계학적으로 유의성 있는 차이를 보이는 결과는 없었다. 결론: 이상의 결과를 통하여 한국인에서 가족력과 무관하게 산발적으로 발생한 난소암 환자 37명에서 1명의 BRCA1 유전자 돌연변이를 확인하였으며 그 발생율은 2.7%이었다. 또한 난소암 감수성 유전자인 BRCA1 및 BRCA2 유전자 다형성과 난소암의 임상병리학적인 특징과는 관련성이 없어 BRCA1 및 BRCA2 유전자 돌연변이는 한국인의 난소암 발생 (carcinogenesis)에 제한된 역할 (limited role)만을 한다고 사료된다.

Objective: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The purposes of this study were firstly to investigate the presence of BRCA1 and BRCA2 mutations in women with non-hereditary ovarian cancer and secondly to evaluate the relationship between ovarian cancer susceptibility gene polymorphism and clinicopathological features. Methods: We studied 37 women who received a diagnosis of sporadic ovarian epithelial cancer and were treated at our hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using PCR-DHPLC-sequencing method. And we examined the relationship between ovarian cancer susceptibility gene polymorphism and clinicopathological features using a high- throughput SNP scoring methods. Results: Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer resulted in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) led to premature termination. She has no family history of breast and ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. Conclusion: Our results were consistent with the concept that there was a limited role of BRCA1 and BRCA2 mutations in ovarian carcinogenesis in Korean population and polymorphisms of some selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer.

Objective: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The purposes of this study were firstly to investigate the presence of BRCA1 and BRCA2 mutations in women with non-hereditary ovarian cancer and secondly to evaluate the relationship between ovarian cancer susceptibility gene polymorphism and clinicopathological features. Methods: We studied 37 women who received a diagnosis of sporadic ovarian epithelial cancer and were treated at our hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using PCR-DHPLC-sequencing method. And we examined the relationship between ovarian cancer susceptibility gene polymorphism and clinicopathological features using a high- throughput SNP scoring methods. Results: Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer resulted in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) led to premature termination. She has no family history of breast and ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. Conclusion: Our results were consistent with the concept that there was a limited role of BRCA1 and BRCA2 mutations in ovarian carcinogenesis in Korean population and polymorphisms of some selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer.

BRCA1, BRCA2, Germline mutation, Sporadic ovarian carcinoma, Polymorphism, BRCA1, BRCA2, Polymorphism