Founder Mutations in the BRCA1 Gene in Polish Families with Breast-Ovarian Cancer

Gorski, B; Byrski, Tomasz; Huzarski, Tomasz; Jakubowska, Anna; Menkiszak, Janusz; Gronwald, Jacek; Płużańska, A; Bębenek, Marek; Fischer-Maliszewska, Ł.; Grzybowska, Ewa; Narod, Steven A.; Lubiński, Jan

doi:10.1086/302922

Cited by 223 publications

(212 citation statements)

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“…This study extends our previous work on familial breast-ovarian cancer in Poland. 11,24 In a previous study, 24 we found one of the 3 common founder BRCA1 mutations in 49 of 364 (13.5%) women with unselected ovarian cancer. Given that the 3 founder mutations are responsible for 91% of BRCA1 mutations, we now estimate the prevalence of all BRCA1 mutations among ovarian cancer cases in Poland to be 14.8%.…”

Section: Discussionmentioning

confidence: 73%

“…Smaller studies, cited in Table V, reported 50 mutations (39%) in 127 families with at least 3 affected relatives. [11][12][13][14][15][16][17]25,30 The proportion of families with BRCA1 mutations in our series is much higher (64%). It is possible that the average family size in the present study is larger than that in the smaller series.…”

Section: Discussionmentioning

confidence: 99%

“…11 Three BRCA1 mutations (5382insC, C61G and 4153delA) are common in Poland, 11 but several other BRCA1 and BRCA2 mutations have also been reported in one or a few families. [11][12][13][14][15][16][17] Our goal was to describe the frequency of BRCA1 and BRCA2 constitutional mutations in a series of 200 breast cancer and breast-ovarian cancer families representing all regions of Poland and to determine the relative contributions of founder and nonfounder mutations. Our study was conducted to advise on national genetic screening policies for the Polish population.…”

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confidence: 99%

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A high proportion of founder BRCA1 mutations in Polish breast cancer families

Górski

Jakubowska

Huzarski

et al. 2004

Intl Journal of Cancer

179

148

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Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and account for the majority of mutations identified to date in Polish breast and breast-ovarian cancer families. It is not known, however, to what extent these 3 founder mutations account for all of the BRCA mutations distributed throughout the country. This question has important implications for health policy and the design of epidemiologic studies. To establish the relative contributions of founder and nonfounder BRCA mutations, we established the entire spectrum of BRCA1 and BRCA2 mutations in a large set of breast-ovarian cancer families with origins in all regions of Poland. We sequenced the entire coding regions of the BRCA1 and BRCA2 genes in 100 Polish families with 3 or more cases of breast cancer and in 100 families with cases of both breast and ovarian cancer. A mutation in BRCA1 or BRCA2 was detected in 66% of breast cancer families and in 63% of breast-ovarian cancer families. Of 129 mutations, 122 (94.6%) were in BRCA1 and 7 (5.4%) were in BRCA2. Of the 122 families with BRCA1 mutations, 119 (97.5%) had a recurrent mutation (i.e., one that was seen in at least 2 families). In particular, 111 families (91.0%) carried one of the 3 common founder mutations. The mutation spectrum was not different between families with and without ovarian cancer. These findings suggest that a rapid and inexpensive assay directed at identifying the 3 common founder mutations will have a sensitivity of 86% compared to a much more costly and labor-intensive full-sequence analysis of both genes. This rapid test will facilitate large-scale national epidemiologic and clinical studies of hereditary breast cancer, potentially including studies of chemoprevention. Germline mutations in BRCA1 (MIM 113-705) and BRCA2 (MIM 600185) account for familial clustering in the majority of families with both breast and ovarian cancers and in approximately one-half of families with site-specific breast cancer. 1-3 Of the more than 1,000 BRCA mutations reported to the Breast Cancer Information Core (BIC) database, many are unique but there are also numerous examples of founder mutations. Founder mutations have been reported in genetic isolates such as Ashkenazi Jews 4,5 and the Icelandic, 6 Finnish, 7 Dutch 8,9 and French Canadian 10 populations. Founder mutations have also been noted in Slavic countries, including Poland. 11 Three BRCA1 mutations (5382insC, C61G and 4153delA) are common in Poland, 11 but several other BRCA1 and BRCA2 mutations have also been reported in one or a few families. 11-17 Our goal was to describe the frequency of BRCA1 and BRCA2 constitutional mutations in a series of 200 breast cancer and breast-ovarian cancer families representing all regions of

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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A high proportion of founder BRCA1 mutations in Polish breast cancer families

Górski

Jakubowska

Huzarski

et al. 2004

Intl Journal of Cancer

179

148

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“…16,17 Ancestry-informed testing of a few common BRCA1/2 mutations has been proposed as a cost-effective approach in a number of populations including Ashkenazi Jews. [18][19][20][21][22][23][24][25] Diagnosing BRCA mutations triggers preventive measures in relatives, which contributes to the value of such screening approaches. 21 The identification of a prevalent founder mutation in a very specific part of the Tyrol may facilitate a long-term study to examine the true sensitivity, usefulness, and cost-effectiveness of routine testing of breast or ovarian cancer patients without any selection based on established HBOC criteria.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

et al. 2015

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Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c. 4183C4T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C4T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region. European Journal of Human Genetics (2016) 24, 258-262; doi:10.1038/ejhg.2015.108; published online 27 May 2015 INTRODUCTIONA central aim of preventive oncology is the identification of patients with a heritable predisposition to cancer. An estimated 1-7% of unselected breast cancer patients 1-4 and 6-17% of women with ovarian cancer 5,6 have hereditary breast and ovarian cancer (HBOC) disposition caused by variants in either BRCA1 or BRCA2 that confer a high risk of developing cancer. In agreement with a widely used terminology, such variants will be called mutations throughout this paper. Because of high costs, comprehensive molecular analyses for HBOC are usually restricted to individuals with a suggestive family history, young age, or several independent tumours. Tumour characteristics (triple-negative breast cancer; TNBC) are also used for the identification of patients with a high probability of carrying a BRCA mutation. 7,8 Reduced costs of novel sequencing methods and better knowledge of the clinical relevance of alterations in BRCA1 and BRCA2 will increase the number of individuals eligible for sequence analysis, although some selection process will still remain necessary in the foreseeable future. Identification of common founder mutations in certain ethnicities allows integration of genetic testing strategies in the routine care of all cancer patients. Here we report the identification of a highly prevalent BRCA1 founder mutation in a particular region of the Tyrol and consider the implications for a screening programme offered to all breast and ovarian cancer patients in this region.

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“…Founder mutations in BRCA1 gene have been recently described in Eastern Baltic Sea region, with variable distribution in Baltic (Latvian [1] and Lithuanian [2]) and Slavic (Polish [3], Belorussian [4], Russian [5]) populations, accounting for 80-90% of all mutations. However, data about its incidence in Lithuania are inconclusive and based on one study where only three mutations were tested in BRCA1 gene [2].…”

Section: Introductionmentioning

confidence: 99%

Novel and common BRCA1 mutations in familial breast/ovarian cancer patients from Lithuania

Janavičius

Pepalytė

Kučinskas

2008

Breast Cancer Res Treat

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Novel and common BRCA1 mutations in familial breast/ovarian cancer patients from LithuaniaRamūnas Janavičius, Ingrida Pepalytė, Vaidutis Kučinskas To cite this version:Ramūnas Janavičius, Ingrida Pepalytė, Vaidutis Kučinskas. Novel and common BRCA1 mutations in familial breast/ovarian cancer patients from Lithuania.

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Founder Mutations in the BRCA1 Gene in Polish Families with Breast-Ovarian Cancer

Cited by 223 publications

References 24 publications

A high proportion of founder BRCA1 mutations in Polish breast cancer families

A high proportion of founder BRCA1 mutations in Polish breast cancer families

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

Novel and common BRCA1 mutations in familial breast/ovarian cancer patients from Lithuania

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