BRCA1 Mutations in a Population-based Study of Breast Cancer in Stockholm County

Abstract

The mutation frequency of BRCA1 and BRCA2 in women with breast cancer varies according to family history, age at diagnosis and ethnicity. The contribution of BRCA1 and BRCA2 mutations in breast cancer populations, unselected for age and family history, has been examined in several studies reporting mutation frequencies between 1% and 12% by screening methods, population sizes, and to what extent the gene/s were screened differed in the studies. We wanted to clarify the proportion of breast cancer attributable to mutations in BRCA1 in an unselected breast cancer population from the Stockholm region. All incident breast cancer patients treated surgically in a 19-month period were eligible for the study and 70% (489/696) participated. Exon 11 of BRCA1 was screened for mutations using the protein truncation test, and the mutation frequency was estimated from that. In previous studies on high-risk families from Stockholm, more than 70% of the mutations were detected in exon 11. Two mutations were found, both in patients with a family history or their own medical history of ovarian cancer, giving a mutation frequency in exon 11 of 0.4% and an estimated BRCA1 mutation frequency of<1%. Mutations in BRCA1 in unselected breast cancer cases in our region are rare and likely to be found only in high-risk families. Our BRCA1 prevalence is the lowest of all studies on unselected breast cancer patients, probably reflecting the comparatively low rates detected also in high-risk breast cancer families from the region.

Estrogen Receptor Beta (ESR2) Polymorphisms in Familial and Sporadic Breast Cancer

“…Our subclassification of families into two groups is consistent with empirical risk estimates, where high-risk families have a 3-5 fold increased risk of developing breast cancer while low-risk families have a 2-3 fold increased risk [24,25]. For all samples from So¨dersjukhuset and Karolinska University Hospital, a family history of breast cancer was obtained and all samples were screened for mutations in BRCA1 exon 11, which accounts for the majority of Swedish mutations [26]. All familial cases from Karolinska Hospital proceeded through genetic counseling and those who met the criteria for BRCA1/2 screening were screened negative for mutations while the remaining samples did not fulfill the criteria necessary for BRCA1 or BRCA2 testing.…”

Contribution of BRCA1 germ-line mutations to breast cancer in Greece: a hospital-based study of 987 unselected breast cancer cases

“…The limited number of studies concerning unselected cases in populations with genetic heterogeneity report a frequency of 1.8 -4.7% for both genes (for a review, see Fackenthal and Olopade (2007)). For BRCA1 only, a mutation frequency of 0.4% is found in Finnish (Syrjakoski et al, 2000), 2.1% in Dutch (Papelard et al, 2000), 3% in Polish (Gorski et al, 2005), o1% in Swedish (Margolin et al, 2004), 1.5% in Brazilian (Gomes et al, 2007), and 2.4 -3.5% in US unselected breast cancer patients (Newman et al, 1998;Malone et al, 2006;John et al, 2007). In our present study, we report a total frequency of 2.6% for the four BRCA1 mutations screened.…”

TGFBR1*6A and Int7G24A variants of transforming growth factor-β receptor 1 in Swedish familial and sporadic breast cancer

“…Population-based cohort Patients with a surgically treated primary invasive breast cancer admitted to the Department of Oncology at Huddinge Hospital and Söder Hospital (covering the population of southern Stockholm of 850 000 people) from October 1998 to May 2000 were asked participate in a study on genetic risk factors from breast cancer (Margolin et al, 2004). Family history, age at diagnosis, hormone receptor status and histology of the tumour were obtained from all cases, and the median follow-up was 5 years.…”