| 1. |
- Einbeigi, Z., et al.
(author)
-
A founder mutation of the BRCA1 gene in Western Sweden associated with a high incidence of breast and ovarian cancer
- 2001
-
In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 37:15, s. 1904-1909
-
Journal article (peer-reviewed)abstract
- 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.
|
|
| 2. |
- Loman, Niklas, et al.
(author)
-
Prognosis and clinical presentation of BRCA2-associated breast cancer
- 2000
-
In: European Journal of Cancer. - 1879-0852. ; 36:11, s. 1365-1373
-
Journal article (peer-reviewed)abstract
- 54 female breast cancer patients from 22 families with BRCA2 germ line mutations from Sweden and Denmark were compared with 214 age- and date of diagnosis-matched controls identified among breast cancer patients from South Sweden. At diagnosis, BRCA2-associated cases were more often node-positive (N+). OR=1.9 (95% confidence interval (CI)=1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6 (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more common among the BRCA2-associated cases: OR=2. 4 (95% CI=1.1-5.3; P=0.027). Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2-associated cases: RR=2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2-associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The unfavourable prognosis in BRCA2-associated breast cancer seems, to a great extent, to be a consequence of the higher clinical stage at diagnosis. The increased presence of bilateral cancers appears to have less impact on survival in this group of hereditary breast cancer. Data presented here needs to be taken into account when counselling healthy carriers of BRCA2 germ line mutations.
|
|
