Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.

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Management of hereditary ovarian cancer

Orvosi Hetilap ◽

10.1556/oh.2011.29218 ◽

2011 ◽

Vol 152 (40) ◽

pp. 1596-1608 ◽

Cited By ~ 2

Author(s):

József Gábor Joó ◽

Szabolcs Ládi ◽

B. Zsolt Nagy ◽

Zoltán Langmár

Keyword(s):

Ovarian Cancer ◽

Hereditary Ovarian Cancer ◽

Brca1 And Brca2 ◽

Ovarian Cancers ◽

Brca2 Mutations ◽

Histological Phenotype ◽

Brca1 Brca2 ◽

Brca1 And Brca2 Mutations ◽

High Level ◽

Associated Tumors

Mutations in BRCA1 and BRCA2 genes account for the majority of hereditary breast and ovarian cancers. Approximately 10% of cases of ovarian cancer are due to germline mutations in BRCA1 and BRCA2. Ovarian cancer associated with BRCA1 and BRCA2 mutations has a distinct histological phenotype. This type of cancer is predominantly of serous or endometrioid histology and is high grade. Patients with BRCA1 or BRCA2 mutations should be offered risk-reducing salpingo-oophorectomy by age 40 years, or when childbearing is complete. Nowadays there are no differences between the treatments provided for sporadic and hereditary ovarian cancer, although there are indications that targeted therapy is effective in women with BRCA1/BRCA2-associated tumors. Retrospective studies reveal a high level of sensitivity to platinum agents in BRCA-associated tumors and initial trials show good efficacy and tolerability for polyADP-ribose polymerase inhibitors in mutation carriers with advanced ovarian cancers. These agents might also potentially be used in chemoprevention. Authors review the current management of hereditary ovarian cancer. Orv. Hetil., 2011, 152, 1596–1608.

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Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

JCO Global Oncology ◽

10.1200/go.21.00051 ◽

2021 ◽

pp. 849-861

Author(s):

Sudeep Gupta ◽

Senthil Rajappa ◽

Suresh Advani ◽

Amit Agarwal ◽

Shyam Aggarwal ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Newly Diagnosed ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Fallopian Tube Cancer ◽

Cross Sectional ◽

Brca2 Mutations ◽

Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

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