A population-based analysis of germline BRCA1 and BRCA2 testing among ovarian cancer patients in an era of histotype-specific approaches to ovarian cancer prevention

Background: Germline BRCA1 or BRCA2 pathogenic variants in ovarian cancer patients may be informative in risk management and treatment, with the advent of poly(ADP-ribose) polymerase inhibitors. In the era of precision medicine, companion diagnostics for BRCA1 and BRCA2 genes have been featured as a strategy in the Malaysia National Strategic Plan for Cancer Control Program (2016-2020). To facilitate this strategy, frequency data from Malaysia's understudied multiethnic population will be required. Aim: To determine the prevalence of BRCA1 and BRCA2 germline variants in a population-based cohort of ovarian cancer patients in Malaysia. Methods: From August 2016, women with nonmucinous epithelial ovarian, peritoneal or fallopian tube carcinoma are prospectively recruited to the Malaysia-wide population-based MaGiC Observational Study. DNA were tested using a Hi-Plex next generation sequencing method and multiplex ligation-dependent probe amplification to detect < 10 bp alterations and exon deletions or duplications in the BRCA1 and BRCA2 genes. Results: Interim results from 325 patients tested until March 2018 have identified BRCA1 and BRCA2 pathogenic variants in 9.8% (32/325) and 3.1% (10/325) patients, respectively. Variants of uncertain significance were detected in 13.2% (43/325) patients and no pathogenic variants were detected in 73.8% (240/325) patients. Taken together, the frequency of BRCA1/2 pathogenic variants in ovarian cancer patients is approximately 12.9% (42/325). Conclusion: The identification of BRCA1 or BRCA2 carriers across the country have enabled the concentration of efforts from limited genetic counseling resources to high risk families. Results arising from the completion of this study will supplement cancer control programs and genetic services in Malaysia.

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TREATMENT AND OUTCOMES OF ELDERLY OVARIAN CANCER PATIENTS: A POPULATION-BASED ANALYSIS

10.26226/morressier.5770e29dd462b80290b4c044 ◽

2016 ◽

Author(s):

Melinda Schuurman

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Population Based

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Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.2.397 ◽

1998 ◽

Vol 16 (2) ◽

pp. 397-404 ◽

Cited By ~ 185

Author(s):

O T Jóhannsson ◽

J Ranstam ◽

A Borg ◽

H Olsson

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Matched Control ◽

Brca1 Mutation ◽

Population Based ◽

Control Group ◽

Breast And Ovarian Cancer ◽

Population Based Study ◽

Matched Control Group ◽

Group Survival

PURPOSE Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.

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A MOLECULAR-BASED APPROACH TO INVESTIGATE BREAST CANCER 1 AND BREAST CANCER 2 STATUS IN OVARIAN CANCER AMONG IRAQI WOMEN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i7.25217 ◽

2018 ◽

Vol 11 (7) ◽

pp. 199

Author(s):

Muhannad Shweash ◽

Saddam Jumaa Naseer ◽

Maisam Khider Al-anii ◽

Thulfiqar Fawwaz Mutar

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Gene Mutations ◽

Healthy Controls ◽

Brca1 And Brca2 ◽

First Degree Relatives ◽

Brca Gene ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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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