Overexpression of BRCA1-IRIS protein in familial ovarian cancers with no BRCA1 or BRCA2 germline mutation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5513-5513
Author(s):  
R. Boustany ◽  
P. Pautier ◽  
A. Rey ◽  
S. Delaloge ◽  
A. Chompret ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Brca2 Mutation ◽  
Point Mutations ◽  
Continuous Variable ◽  
Wilcoxon Test ◽  
Brca1 And Brca2 ◽  
Ovarian Carcinomas ◽  
Ovarian Cancers ◽  
History Of

5513 Background: Germline mutations of the BRCA1 and BRCA2 genes account for the majority of hereditary breast-ovarian carcinomas. Nevertheless, in some patients with family history of ovarian cancers, neither point mutations nor genomic alterations are identified. Recently, IRIS gene, an open reading frame that extended from codon 1 of BRCA1 to a termination point in intron 11, has been identified. The encoded protein has been reported to play a role in controlling the replication origins firing (ROF) pathway. The study presented here aims at characterizing whether ROF-related proteins are differentially expressed among familial ovarian cancers associated with a germline BRCA1 or 2 mutation, familial ovarian cancers with wild-type BRCA1/2 genes, and sporadic ovarian cancers. Methods: Tumor samples from 72 patients with ovarian cancer and screened for BRCA1 and BRCA2 mutation because of family history of breast/ovarian cancer were collected. These cases were matched with 134 sporadic ovarian cancers (controls) according to age, year of diagnosis, tumor stage, histological subtype, and grade. The cases distributed among 26 BRCA1-linked (BRCA1*) tumors, 9 BRCA2-linked (BRCA2*) tumors and 37 with no identified mutation (BRCA1wt/BRCA2wt). Tissue micro-arrays were prepared from the paraffin blocks. P53, MCM3, MCM4, Geminin, PTTG and BRCA1-IRIS immuno-expression were scored with no information on the sample group as follows: the final score was the product of the positive cells percentage by the staining intensity, the final result being used as a continuous variable. Differences between cases and controls were tested by a Wilcoxon test for paired samples. Results: IRIS expression was significantly higher in familial cancers than in controls (P=0.002). When BRCA1/2 genes status was taken into account, differences remained significant when BRCA1wt/BRCA2wt tumors (P=0.04), but not when BRCA1* tumors were compared with controls. However, the latter showed significant higher expression of Geminin than controls (P=0.04). Conclusions: BRCA-1 IRIS protein is overaccumulated in ovarian cancers developed by patients with family history. Our results suggest IRIS may play a role in the development of ovarian cancers and could be related with an ovarian susceptibility. No significant financial relationships to disclose.

scholarly journals Ovarian tumor: a review

2021 ◽  
Vol 10 (9) ◽  
pp. 3657
Author(s):  
Poonam Kashyap
Keyword(s):  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Screening Method ◽  
Progression Free Survival ◽  
Angiogenesis Inhibitors ◽  
Parp Inhibitors ◽  
Brca1 And Brca2 ◽  
Elderly Age ◽  
Ovarian Cancers ◽  
History Of

Ovarian cancers are the 7th most common cancers in women. It is found more commonly in elderly age group. The survival depends on the stage of diagnosis and many of the patients present in advanced disease when the prognosis becomes dismal. The dilemma is to differentiate them from benign disease so that the unwanted laparotomies could be saved. Biomarkers and radiological classification may play a role in differentiating benign from malignant and deciding on the management. There is no screening method to diagnose ovarian cancers and the patient presents with nonspecific complaints missing them in early stages. Optimal cytoreduction is required for better overall survival, progression free survival and response to adjuvant chemotherapy. Those women having history of breast, ovary, endometrial, colorectal cancers should be screened for malignancies and genetic testing is advised. Surgery is the mainstay of treatment followed by chemotherapy. Risk reducing salpingoophorectomy can be offered to women having BRCA1 and BRCA2 mutation carriers after they complete their family. The area of target therapies is the most recent and promising in treatment of ovarian cancer. They are coming in forefront when chemotherapy toxicity, drug resistance are big hurdles in treatment of ovarian cancer. With recent advances and understanding of the biology of ovarian cancer have led to clinical trials of targeted agents. The  angiogenesis inhibitors and polyadenosine diphosphate-ribose polymerase (PARP) inhibitors are the most developed.

Genetic risk factors for familial ovarian cancer

2002 ◽  
Vol 8 (3) ◽  
pp. 92-97
Author(s):  
Elmar Stickeler ◽  
Ingo B Runnebaum
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Individual Risk ◽  
Ovarian Cancer Risk ◽  
Cancer Syndrome ◽  
Brca1 And Brca2 ◽  
Ovarian Cancers ◽  
Mutation Carriers

In Europe ovarian cancer represents the third most common cancer of the female genital tract, with 30,000 newly diagnosed patients per year. Family history is the most significant risk factor. Lifetime risk for ovarian cancer increases from 1.4% for women with a negative family history to 14.6-32.2% in women from affected families. About 5-10% of ovarian cancers are hereditary and supposed to occur in three different forms: hereditary breast and ovarian cancer syndrome (HBOC), site-specific hereditary ovarian cancer (HOC) and hereditary nonpolyposis colorectal cancer syndrome (HNPCC). HBOC and HOC account for 80-90% of the cases and are associated with inactivating germline mutations of the BRCA1 and BRCA2 genes. For BRCA1 and BRCA2 mutation carriers the cumulative risk by age 70 of developing ovarian cancer is 45-60% and 25-30%, respectively. Approximately 10-15% of familial ovarian cancers are related to the HNPCC syndrome with a cumulative ovarian cancer risk of 9% by age 70. Germline polymorphisms may further modify ovarian cancer risk. Bilateral prophylactic oophorectomy reduces the risk of developing ovarian cancer in HBOC and HOC families by 50%. Tubal ligation also significantly reduces the risk in BRCA1 mutation carriers (odds ratio 0.39). Knowledge of the genetic background provides an objective basis for individual risk assessment and prevention.

Moving Toward Personalized Medicine: Treatment-Focused Genetic Testing of Women Newly Diagnosed With Ovarian Cancer

2010 ◽  
Vol 20 (5) ◽  
pp. 704-716 ◽  
Author(s):  
Alison H. Trainer ◽  
Bettina Meiser ◽  
Kaaren Watts ◽  
Gillian Mitchell ◽  
Kathy Tucker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Mutation Frequency ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Age At Onset ◽  
Prognostic Significance ◽  
Brca1 And Brca2 ◽  
Germline Brca Mutation

Objectives:The presence of a germline BRCA mutation defines a genotype-specific group of women whose invasive ovarian cancer is associated with an increasingly well-defined prognostic and chemosensitivity biological profile. To determine the criteria that may be used to select patients for BRCA treatment-focused genetic testing, we performed a systemic literature search of studies that assessed BRCA1 and BRCA2 mutation frequency in women with ovarian cancer unselected for family history. The results are discussed with regard to the added clinical value gained by identifying a germline BRCA mutation at the time of the ovarian cancer diagnosis.Methods:BRCA-related studies were identified in the CD-ROM databases PubMed (including MEDLINE), PsychINFO, and CINAHL and included in the review if they met the following criteria: they (a) assessed mutation frequency in women with ovarian cancer who were unselected for family history and ethnicity, (b) were published in a peer-review journal, (c) between January 1997 and October 2009, and (d) in the English language.Results:Studies investigating the prevalence of BRCA1 or BRCA2 mutations in ovarian cancer patients unselected for family history or ethnicity have found a pathological BRCA mutation rate of approximately 3% to 17%. Without a significant family history, specific features that may be used to target treatment-focused BRCA testing in the ovarian cancer setting include young age at onset (<50 years), high-grade serous tumor histology, and specific ethnicity associated with known BRCA founder mutations.Conclusions:We believe that given the growing appreciation of the prognostic significance of BRCA mutations and the differential chemosensitivity shown by these tumors, as well as the potential of novel agents such as poly(ADP-ribose) polymerase inhibitors, the identification of a germline BRCA mutation concurrent with a new diagnosis of ovarian cancer will significantly impact on tailoring personalized ovarian management in the future.

Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 31 (33) ◽  
pp. 4188-4198 ◽  
Author(s):  
Patricia G. Moorman ◽  
Laura J. Havrilesky ◽  
Jennifer M. Gierisch ◽  
Remy R. Coeytaux ◽  
William J. Lowery ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Ovarian Cancer Risk ◽  
Mutation Carriers ◽  
History Of ◽  
Meta Analyses

Purpose To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. Methods We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. Results From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. Conclusion Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

Contribution of BRCA1 and BRCA2 mutations to breast cancer in Tunisia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22191-e22191
Author(s):  
T. Wafa
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Hereditary Breast Cancer ◽  
Brca2 Mutation ◽  
Brca2 Gene ◽  
Brca1 Gene ◽  
Deleterious Mutations ◽  
Brca1 And Brca2 ◽  
Frameshift Mutations ◽  
History Of

e22191 Background: Hereditary breast cancer accounts for 3–8% of all breast cancers. It was recently estimated that a combination of BRCA1 and BRCA2 genes mutations is responsible for 30% of hereditary breast cancer cases. Methods: To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, 36 patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. Thirty three patients are suggestive of BRCA1 mutation and 3 are suggestive of BRCA2 mutation. Results: Four mutations in BRCA1 gene were described among which, one novel splice site mutation (330 dupA) and 3 frameshift mutations including the 4160 delAG, the 2789 delG and the 5385 insC. Our study is the first to describe the 5385 insC mutation which was described only among Jewish Ashkenazi population. Two frameshift mutations (1537 del4 and 5909 insA) were screened in BRCA2 gene. Nineteen percent (7/36) of the familial cases were altered on BRCA1 or BRCA2 genes with deleterious mutations at heterozygous state and 55% (20/36) by mutation with uncertain value (UV) or by single nucleotide polymorphisms (SNPs). Conclusions: Almost all the cases mutated by deleterious mutations on BRCA1 gene reported a family history of breast and/or ovarian cancer in the index case or in their relatives. On the contrary, patients with an UV mutation or SNPs have no history of ovarian cancer in their corresponding families. Our data are the first to contribute to information on mutation spectrum of BRCA genes and offer a recommended screening mode for clinical genetic testing policy in Tunisia. No significant financial relationships to disclose.

scholarly journals Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation

2008 ◽  
Vol 100 (2) ◽  
pp. 421-425 ◽  
Author(s):  
K A Metcalfe ◽  
A Finch ◽  
A Poll ◽  
D Horsman ◽  
C Kim-Sing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Brca2 Mutation ◽  
Cancer Risks ◽  
History Of

scholarly journals EPITHELIAL OVARIAN CANCER;

2012 ◽  
Vol 19 (01) ◽  
pp. 040-045
Author(s):  
SARAH SAEED ◽  
MOHAMMAD AKRAM
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Epithelial Ovarian Cancer ◽  
Positive Family History ◽  
Striking Feature ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
University Of Toronto ◽  
Number Of Patients ◽  
History Of

Background: Epithelial ovarian cancer is the most common cancer of gynaecologic origin in Pakistani women. It ranks amongthe ten most common cancers in our women. Despite being commonly encountered, information regarding the clinicopathological features islacking. Objective: To study the clinical and pathological features of epithelial ovarian cancer in our patients. Study Design: Retrospective study.Setting: Department of Medical Oncology, Jinnah Hospital Lahore. Period: Jan 01,2001 to Dec 31, 2002. Patients and methods: All patientswith histological or cytological diagnosis of epithelial ovarian cancer regardless of stage were included in the study. Information was obtainedfrom medical records which were reviewed thoroughly. Blood samples for analysis of BRCA mutations were sent to University of Toronto,Sunnybrook & Women’s College Health Sciences Centre, Toronto, Canada. Results: 75 patients were accrued. Mean age of the patients was47 years. The well defined risk factors such as nulliparity, lack of lactation, early menarche and late menopause were not present in the majorityof our patients. One striking feature was the number of patients with family history of cancer (18.7%). Majority were first degree relatives of thepatients and most had ovarian or breast cancer. BRCA1 and BRCA2 were seen in nine (12%) of the patients. Clinical presentation and histologicfeatures were similar to American and European patients, the only difference was that a large number (88%) of our patients presented withadvanced (stage III or IV) disease. Conclusions: Epithelial ovarian cancer manifests itself in a younger population of our women. Higherfrequency of positive family history was another striking feature of Pakistani patients.

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