High Frequency of BRCA1 and BRCA2 Germline Mutations in Ashkenazi Jewish Ovarian Cancer Patients, Regardless of Family History

Beller, Uziel; Halle, David; Catane, Raphael; Kaufman, Brian; Hornreich, Gila; Levy‐Lahad, Ephrat

doi:10.1006/gyno.1997.4844

Cited by 77 publications

(26 citation statements)

References 22 publications

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“…The study was restricted to patients of Jewish origin because of the relative ease of BRCA1 and BRCA2 genotyping as a result of the existence of 3 common founder (ancient) mutations in this ethnic group (see below), and the relatively large fraction of ovarian cancer cases that are linked to BRCA in the Ashkenazim (45%-48%). 15,16 Archival pathological tissue specimens were accessioned from hospital tissue banks for each of the 189 cases. Clinical and pathological information, including age at diagnosis, date of primary surgery, residual disease following primary surgery (optimal or suboptimal), surgical stage, histologic cell type and grade, time to recurrence following chemotherapy, and clinical status at last follow-up were abstracted from hospital records.…”

Section: Subjectsmentioning

confidence: 99%

Clinicopathologic Features of <EMPH TYPE="ITAL">BRCA</EMPH>-Linked and Sporadic Ovarian Cancer

Boyd

Sonoda²,

Federici³

et al. 2000

JAMA

499

292

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Context Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival.Objective To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. Design and SettingRetrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PatientsThe study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison.Main Outcome Measures Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advancedstage (III and IV) cases. ResultsHereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1-vs BRCA2-linked patients (54 vs 62 years; P= .04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (PϽ.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P = .03). ConclusionsAlthough BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advancedstage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

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Section: Subjectsmentioning

confidence: 99%

Clinicopathologic Features of <EMPH TYPE="ITAL">BRCA</EMPH>-Linked and Sporadic Ovarian Cancer

Boyd

Sonoda²,

Federici³

et al. 2000

JAMA

499

292

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“…[17][18][19][20][21] Young women of Ashkenazi Jewish descent appear to be at particularly high risk because of the prevalence of the BRCA1 mutation 185 del AG. 22,23 Prophylactic oophorectomy, despite some controversy, 24,25 is performed currently in numerous medical centers, [25][26][27] because it is considered a means to improve patient survival and is cost effective. 6,22 Alpha: nuclear area; beta: beta coefficient (for full description, see text).…”

Section: Discussionmentioning

confidence: 99%

Ovarian dysplasia in prophylactic oophorectomy specimens

Deligdisch

Gil

Kerner³

et al. 1999

Cancer

100

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“…In Iceland, a single mutation found in the BRCA2 gene is responsible for the majority of cases of hereditary breast cancer. In the Ashkenazi Jewish population, however, a very high rate has been reported for the following three mutations: 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 (16,20).…”

Section: Discussionmentioning

confidence: 99%

Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil

Esteves

Thuler

Amendola

et al. 2009

Braz J Med Biol Res

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Of all malignant neoplasias affecting women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to determine the frequency of genetic modifications in families with medium and high risk for breast and ovarian cancer from different regions of Brazil. An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high-risk families for breast and/or ovarian cancer. After heredogram construction, a blood sample was taken and DNA extraction was performed in all index cases. The protein truncation test was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Of the 612 individuals submitted to genetic testing, 21 (3.4%), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. Of the 19 BRCA1 mutations found in the 18 participants, 7 consisted of ins6kb mutations, 4 were 5382insC, 3 were 2156delGinsCC, 2 were 185delAG, 1 was C1201G, 1 was C3522T, and 1 was 3450del4. With respect to the BRCA2 gene, 3 mutations were found: 5878del10, 5036delA and 4232insA (one case each). The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies on high-risk Brazilian populations. The inclusion of individuals with medium risk may have contributed to the lower prevalence observed.

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High Frequency of BRCA1 and BRCA2 Germline Mutations in Ashkenazi Jewish Ovarian Cancer Patients, Regardless of Family History

Cited by 77 publications

References 22 publications

Clinicopathologic Features of <EMPH TYPE="ITAL">BRCA</EMPH>-Linked and Sporadic Ovarian Cancer

Clinicopathologic Features of <EMPH TYPE="ITAL">BRCA</EMPH>-Linked and Sporadic Ovarian Cancer

Ovarian dysplasia in prophylactic oophorectomy specimens

Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil

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