Elsevier

The Lancet

Volume 347, Issue 9016, 15 June 1996, Pages 1643-1645
The Lancet

Articles
Germline BRCA1 185delAG mutations in Jewish women with breast cancer

https://doi.org/10.1016/S0140-6736(96)91484-1Get rights and content

Abstract

Summary

Background We aimed to find out the proportion of breast cancers in Ashkenazi Jewish women attributable to the frameshift mutation at position 185 involving the deletion of adenine and guanine (185delAG) in the breast cancer gene BRCA1.

Methods We studied 107 Ashkenazi Jewish women with breast cancer seen at medical oncology and genetic counselling clinics in New York over a three and a half year period beginning in 1992. 80 of the women were diagnosed before age 42 years; the other 27 were diagnosed between 42 and 50 years and had a positive family history. Genomic DNA testing by PCR amplification was done to identify any 185delAG mutations of the BRCA1 gene.

Findings Of the 80 women diagnosed before the age of 42 years, 16 (20%, 95% Cl 11·2-28·8) were heterozygous for the mutation. All 16 women had at least one first-degree or second-degree relative with breast or ovarian cancer. Of 27 probands diagnosed with breast cancer between the ages of 42 and 50 years who had at least one first-degree relative affected with breast or ovarian cancer, 8 (30%, 95% Cl 12-47) had 185delAG mutations.

Interpretation These data suggest that screening for the 185delAG mutation may be useful in genetic counselling of these women where options for detection and prevention of possible cancers can be discussed.

References (12)

  • D. Ford et al.

    Risks of cancer in BRCA1-mutation carriers

    Lancet

    (1994)
  • Shattuck-Eidens D, McClure M, Simard J, et al. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian...
  • J. Simard et al.

    Recurrent mutations of the BRCA1 gene in Canadian breast and ovarian cancer families

    Nature Genet

    (1994)
  • Jp Struewing et al.

    Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer

    Am J Hum Genet

    (1995)
  • F. Tonin et al.

    Germline mutation of BRCA1 in Ashkenazi Jewish women

    Am J Hum Genet

    (1995)
There are more references available in the full text version of this article.

Cited by (137)

  • Disparities in Breast Cancer Outcomes and How to Resolve Them

    2023, Hematology/Oncology Clinics of North America
    Citation Excerpt :

    It is estimated that 5% to 10% of breast cancers present in individuals with familial inheritance of susceptibility.27 Most are autosomal dominant and highly penetrant.28 Patients with these mutations are often younger at diagnosis and have a higher grade, more aggressive disease.

  • Germline Testing for Individuals with Pancreatic Adenocarcinoma and Novel Genetic Risk Factors

    2022, Hematology/Oncology Clinics of North America
    Citation Excerpt :

    BRCA2 mutations are the single most common germline genetic finding in patients with PDAC, contributing to 10% to 20% of all PDAC cases in familial PDAC21–24 and to 1% to 8% of unselected PDAC cases.2,3,25,26 The population-based prevalence of BRCA1 or BRCA2 mutations is estimated around 1 in 400,27 although founder mutations lead to a higher prevalence in some populations such as the Ashkenazi Jews.28 The relative risk of PDAC ranges from 3- to 6-fold in BRCA2 mutation carriers with a lifetime risk estimated at 4% to 8%.20,29

  • Disparities in Breast Cancer

    2022, Obstetrics and Gynecology Clinics of North America
  • A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: Referral indications for cancer predisposition assessment

    2015, Genetics in Medicine
    Citation Excerpt :

    Of males with breast cancer, 15–20% have a BRCA1/2 mutation.63 The overall prevalence of BRCA1 mutations is estimated at 1 in 300 and that of BRCA2 mutations is estimated at 1 in 800, but founder mutations in many populations (e.g., Ashkenazi Jewish,64,65,66,67 Icelandic,68 and Mexican Hispanic69 populations) lead to increased mutation prevalence in these populations. Referral should be considered for any individual with a personal history of or first-degree relative with (i) breast cancer diagnosed at or before age 50; (ii) triple-negative breast cancer diagnosed at or before age 60; (iii) two or more primary breast cancers in the same person; (iv) ovarian, Fallopian tube, or primary peritoneal cancer; (v) Ashkenazi Jewish ancestry and breast or pancreatic cancer at any age; or (vi) male breast cancer.

View all citing articles on Scopus
View full text