A founder mutation of the BRCA1 gene in Western Sweden associated with a high incidence of breast and ovarian cancer

• The aim of this study was to describe and characterise a founder mutation of the BRCA1 gene in western Sweden. Of 62 families screened for BRCA mutations, 24 had BRCA1 mutations and two had BRCA2 mutations. Tumours that occurred in family members were histologically reviewed and mutational status was analysed using archival paraffin-embedded tissues. The same BRCA1 mutation, 3171ins5, was found in 16 families who were clustered along the western coast of Sweden. Mutation analysis revealed a maternal linkage in 13 families and a paternal linkage in 3. There was complete agreement between mutation analysis results obtained from blood and archival tissues. The penetrance of breast or ovarian cancer by age 70 years was estimated to be between 59 and 93%. There were no differences in survivals between breast or ovarian cancer patients with the mutation and age-matched controls. Thus, a predominant BRCA1 gene founder mutation associated with a high risk of breast and ovarian cancer has been identified and found to occur in a restricted geographical area, thereby allowing timely and cost-effective mutation screening using blood samples or archival histological material. 

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

BRCA1 gene

Breast neoplasms

Founder effect

Ovarian neoplasms

BRCA1 protein

BRCA2 protein

paraffin

adult

age

aged

article

blood sampling

breast carcinoma

cancer incidence

cancer patient

cancer survival

controlled study

cost effectiveness analysis

disease association

female

gene mutation

genetic analysis

genetic linkage

genetic screening

geographic distribution

high risk population

histopathology

human

human tissue

major clinical study

ovary carcinoma

penetrance

priority journal

Sweden

DNA Mutational Analysis

Genes

BRCA1

Humans

Incidence

Middle Aged

Multivariate Analysis

Mutation

Neoplastic Syndromes

Hereditary

Polymerase Chain Reaction

Risk Assessment

Survival Rate

Publication and Content Type

ref (subject category)

art (subject category)