Founder BRCA 1 and 2 mutations among a consecutive series of ashkenazi Jewish ovarian cancer patients

Daniel Tobias, Christine Eng, Leslie D. McCurdy, Tamara Kalir, John Mandelli, Peter R. Dottino, Carmel J. Cohen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objective. The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. Materials and methods. From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-μm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the X(2) test or a two-tailed Fisher's-exact test, depending on the sample size. Results. There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insc mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represented a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59%) compared to those without at least one affected first degree relative (10/70 or 14%) was highly significant (P = 0.001). Conclusions. Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)148-151
Number of pages4
JournalGynecologic Oncology
Volume78
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Mutation
Multiplex Polymerase Chain Reaction
Incidence
Chemoprevention
Genetic Testing
Parity
Paraffin
Sample Size
Histology

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

Cite this

Tobias, Daniel ; Eng, Christine ; McCurdy, Leslie D. ; Kalir, Tamara ; Mandelli, John ; Dottino, Peter R. ; Cohen, Carmel J. / Founder BRCA 1 and 2 mutations among a consecutive series of ashkenazi Jewish ovarian cancer patients. In: Gynecologic Oncology. 2000 ; Vol. 78, No. 2. pp. 148-151.
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title = "Founder BRCA 1 and 2 mutations among a consecutive series of ashkenazi Jewish ovarian cancer patients",
abstract = "Objective. The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. Materials and methods. From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-μm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the X(2) test or a two-tailed Fisher's-exact test, depending on the sample size. Results. There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insc mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30{\%}, respectively). This represented a 25{\%} incidence (95{\%} CI: 16-34{\%}) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59{\%}) compared to those without at least one affected first degree relative (10/70 or 14{\%}) was highly significant (P = 0.001). Conclusions. Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures. (C) 2000 Academic Press.",
author = "Daniel Tobias and Christine Eng and McCurdy, {Leslie D.} and Tamara Kalir and John Mandelli and Dottino, {Peter R.} and Cohen, {Carmel J.}",
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Founder BRCA 1 and 2 mutations among a consecutive series of ashkenazi Jewish ovarian cancer patients. / Tobias, Daniel; Eng, Christine; McCurdy, Leslie D.; Kalir, Tamara; Mandelli, John; Dottino, Peter R.; Cohen, Carmel J.

In: Gynecologic Oncology, Vol. 78, No. 2, 01.01.2000, p. 148-151.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Founder BRCA 1 and 2 mutations among a consecutive series of ashkenazi Jewish ovarian cancer patients

AU - Tobias, Daniel

AU - Eng, Christine

AU - McCurdy, Leslie D.

AU - Kalir, Tamara

AU - Mandelli, John

AU - Dottino, Peter R.

AU - Cohen, Carmel J.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Objective. The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. Materials and methods. From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-μm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the X(2) test or a two-tailed Fisher's-exact test, depending on the sample size. Results. There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insc mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represented a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59%) compared to those without at least one affected first degree relative (10/70 or 14%) was highly significant (P = 0.001). Conclusions. Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures. (C) 2000 Academic Press.

AB - Objective. The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. Materials and methods. From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-μm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the X(2) test or a two-tailed Fisher's-exact test, depending on the sample size. Results. There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insc mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represented a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59%) compared to those without at least one affected first degree relative (10/70 or 14%) was highly significant (P = 0.001). Conclusions. Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures. (C) 2000 Academic Press.

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