Mutational Analysis of BRCA 1 and BRCA 2 and Clinicopathologic Analysis of Ovarian Cancer in 82 Ovarian Cancer Families : Two Common Founder Mutations of BRCA 1 in Japanese Population 1

Department of Obstetrics and Gynecology [M. S., H. N., K. T.] and Neurology [S. T.], Niigata University, School of Medicine, Niigata 951-8510; Department of Gynecology, Cancer Institute Hospital, Tokyo 170-8455 [Y. H.]; Department of Obstetrics and Gynecology, Hokkaido University, School of Medicine, Hokkaido 060-8638 [S. F.]; Department of Obstetrics and Gynecology, Kagoshima City Hospital, Kagoshima 892-8580 [M. H.]; Department of Obstetrics and Gynecology, Nagoya Daini Red Cross Hospital, Aichi 466-8650 [I. K.]; Department of Obstetrics and Gynecology, National Kure Medical Center, Hiroshima 737-0023 [T. F.]; Department of Obstetrics and Gynecology, National Defense Medical College, Saitama 359-8513 [I. N.]; Department of Obstetrics and Gynecology, Kurume University, School of Medicine, Fukuoka 830-0011 [K. U.]; Department of Obstetrics and Gynecology, Kinki University, School of Medicine, Osaka 589-8511 [K. O.]; Department of Obstetrics and Gynecology, Jichi Medical School, Tochigi 329-0498 [M. S.]; Department of Obstetrics and Gynecology, Kagoshima University, School of Medicine, Kagoshima 890-8520 [M. Y.]; Department of Obstetrics and Gynecology, Osaka City University, School of Medicine, Osaka 545-8585 [N. U.]; Department of Obstetrics and Gynecology, Tohoku University, School of Medicine, Miyagi 9808575 [S. S.]; Department of Obstetrics and Gynecology, Osaka University, School of Medicine, Osaka 565-0871 [T. E.]; and Department of Obstetrics and Gynecology, Kobe University, School of Medicine, Hyogo 650-0017 [S. M.], Japan ABSTRACT We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian can-