A BRCA1 founder mutation, identified with haplotype analysis, allowing genotype/phenotype determination and predictive testing

We searched for a founder mutation in a population from one geographic region of Norway with prevalent breast/ovarian cancer families. We sampled 33 breast/ovarian cancer families and determined haplotypes of four markers linked to the BRCA1 region. Of the affected 33 index women, 13 (39.4%) shared one haplotype. In five (15% of total), an identical mutation was indicated by an abnormal truncated protein test (PTT) of exon 11 and shown to represent a 1675delA mutation. In the other index women, PTT of exon 11 showed no abnormality. No other BRCA1 founder mutation of this prevalence is likely because no other haplotype was more frequent in affecteds than in controls. All families with the 1675delA mutation in this geographic region may be considered as part of one large kindred. This allows a genotype-phenotype correlation to be precisely determined and used in genetic counselling for predictive testing within this kindred. Identification of identical haplotypes between unrelated affected individuals may be used to estimate the extent of founder effects for any mapped disease, without knowledge of the specific founder mutation. (C) 1997 Elsevier Science Ltd

PREDICTORS OF SURVIVAL IN PATIENTS WITH RECURRENT OVARIAN CANCER UNDERGOING SECONDARY CYTOREDUCTIVE SURGERY BASED ON AN INTERNATIONAL COLLABORATIVE ANALYSIS

PREDICTORS OF SURVIVAL IN PATIENTS WITH RECURRENT OVARIAN CANCER UNDERGOING SECONDARY CYTOREDUCTIVE SURGERY BASED ON AN INTERNATIONAL COLLABORATIVE ANALYSIS R.-Y. Zang1, P. Harter2, D.S. Chi3, J. Sehouli4, R. Jiang1, C.G. Tropé5, A. Ayhan6, G. Cormio7, Y. Xing8, K. Wollschlaeger9, E.I. Braicu4, C.A. Rabbitt3, H. Oksefjell5, W.-J. Tian1, C. Fotopoulou4, J. Pfisterer10, A. du Bois2, J.S. Berek11 1Ovarian Cancer Program, Department of Gynecologic Oncology, Fudan University Cancer Hospital, Shanghai, China, 2Department of Gynecology & Gynecologic Oncology, HSK, Dr. Horst Schmidt Klinik, Wiesbaden, Germany, 3Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 4Department of Gynecology, Charité Medical University of Berlin, Berlin, Germany, 5Division of Gynecology and Obstetrics, Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway, 6Department of Obstetrics and Gynecology, Baskent University Faculty of Medicine, Ankara, Turkey, 7Department of Gynecology, Obstetrics and Neonatology, University of Bari, Bari, Italy, 8Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 9Department of Gynecology and Obstetrics, University of Magdeburg, Magdeburg, 10Department of Gynecology and Obstetrics, Hospital Solingen, Solingen, Germany, 11Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1,100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analyzed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared to 27.0 months in those with residual disease of 0.1-1cm and 15.6 months in those with residual disease of >1cm, respectively (P< 0.0001). Progression-free interval (< 23.1 months vs. >=23.1 months, hazard ratio (HR),1.72; score: 2), ascites at recurrence (present vs. absent, HR, 1.27; score: 1), extent of recurrence (multiple vs. localized disease, HR, 1.38; score: 1) as well as residual disease after SCR (R1 vs. R0, HR, 1.90, score: 2; R2 vs. R0, HR,3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer