This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

Baruch Modan, MD; Eva Gak, PhD; Revital Bar Sade-Bruchim, MSc; Galit Hirsh-Yechezkel, MSc; Livia Theodor, PhD; Flora Lubin, MSc; Gilad Ben-Baruch, MD; Uzi Beller, MD; Amiram Fishman, MD; Ram Dgani, MD; Joseph Menczer, MD; Moshe Papa, MD; Eitan Friedman, MD, PhD

JAMA. 1996;276(22):1823-1825.

Abstract
Objective.
—To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis.

Design.
—Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls.

Setting.
—A community-based case-control incidence study.

Subjects.
—Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation.

Main Outcome Measures.
—Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses.

Results.
—The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (±SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases—50 (±1.4) vs 60.5 (±3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01).

Conclusions.
—Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer.

Author Affiliations
for the National Israel Study of Ovarian Cancer

From the Department of Clinical Epidemiology (Drs Modan and Gak and Mss Hirsh-Yechezkel and Lubin), the Oncogenetics Unit (Ms Sade-Bruchim and Drs Theodor and Friedman), the Department of Surgery (Dr Papa), and the Gynecological Oncology Unit (Dr Ben-Baruch), Chaim Sheba Medical Center, Tel Hashomer, Israel; the Stanley Steyer Institute for Cancer Epidemiology and Research, Tel Aviv University, Tel Aviv, Israel (Dr Modan and Ms Lubin); Shaare Zedek Medical Center, Jerusalem, Israel (Dr Beller); Sapir Medical Center, Kfar Saba, Israel (Dr Fishman); Kaplan Medical Center, Rehovot, Israel (Dr Dgani); and the Edith Wolfson Medical Center, Holon, Israel (Dr Menczer).

Footnotes
A complete list of the National Israel Study of Ovarian Cancer participants appears at the end of this article.

Reprints: Baruch Modan, MD, Department of Clinical Epidemiology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada
Risch et al.
JNCI J Natl Cancer Inst 2006;98:1694-1706.
ABSTRACT | FULL TEXT  

Cancer Incidence in a Population of Jewish Women at Risk of Ovarian Cancer
Liede et al.
JCO 2002;20:1570-1577.
ABSTRACT | FULL TEXT  

Parity, Oral Contraceptives, and the Risk of Ovarian Cancer among Carriers and Noncarriers of a BRCA1 or BRCA2 Mutation
Modan et al.
NEJM 2001;345:235-240.
ABSTRACT | FULL TEXT  

Genetically Tailored Preventive Strategies: an Effective Plan for the Twenty-first Century?
Li and Whittemore
Cancer Epidemiol. Biomarkers Prev. 1999;8:649-658.
ABSTRACT | FULL TEXT  

BRCA1 Mutations and Survival in Women with Ovarian Cancer
Cannistra et al.
NEJM 1997;336:1254-1257.
FULL TEXT  

BRCA1 Mutations in Women With Ovarian Cancer
Shushan et al.
JAMA 1997;277:963-963.
ABSTRACT  

BRCA1 Mutation Is Common in Israelis with Ovarian Cancer
JWatch Women's Health 1997;1997:10-10.
FULL TEXT