Frequency of BRCA1 Mutation 5382insC in German Breast Cancer Patients

Backe, J.; Hofferbert, Sigrun; Skawran, Britta; Dörk, Thilo; Stuhrmann, Manfred; Karstens, Johann H.; Untch, Michael; Meindl, Alfons; Burgemeister, Renate; Chang‐Claude, Jenny; Weber, Bernhard H. F.

doi:10.1006/gyno.1998.5270

Cited by 67 publications

(41 citation statements)

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“…Mutation BRCA1 5382insC, for example, is the second most recurrent mutation reported in the BRCA1 gene according to the BIC and has been identified in several countries, such as Russia, Poland, the Czech Republic, Lithuania, Hungary, Greece, Germany, France, Italy, Canada, and Spain, suggesting that this mutation could have existed before the Jewish diaspora [2]. In Latin America, the same mutation has been identified as a founder in Argentina and Brazil, so it is believed that this mutation likely originated in the Baltic zone at least 38 generations ago, with a gradual descent from East to West, according to haplotype analyses indicating a single founder effect for this mutation that occurred for both Europe and North America [40]. Mutation BRCA1 185delAG has been reported as a founder in Argentinian people, whereas it has also been reported as recurrent in Brazil, Chile, and recently Peru and Mexico.…”

Section: Discussionmentioning

confidence: 96%

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Ossa

Torres

2016

The Oncologist

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Background. Numerous epidemiological factors affect the probability of developing breast or ovarian cancer, but no predictor is as determinant as inheriting a mutation in BRCA1 or BRCA2. The concept of the founder effect explains the reduced genetic variability in some populations, according to the theory that new populations can be formed from a reduced number of individuals, so the new population would carry only a small fraction of the genetic variability of the original population. The main purpose of this review is to provide an update on the state of the art in founder mutations and some recurrent mutations that have recently been described in Latin America. Methods. A literature search was performed in the electronic databases of PUBMED, EMBASE, LILACS, and BIREME using the terms BRCA1, BRCA2, founder mutation, Latin American population, and Hispanic. Sixty-two papers were identified, of which 38 were considered relevant for this review. Each result is shown per country. Results. In Latin America, clear founder effects have been reported in Mexico (BRCA1 del exons 9-12), Brazil (BRCA1 5382insC and BRCA2 c.156_157insAlu), and Colombia (BRCA1 3450del4, A1708E, and BRCA2 3034del4) and in Latinas residing

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Section: Discussionmentioning

confidence: 96%

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Ossa

Torres

2016

The Oncologist

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Section: Patientsmentioning

confidence: 99%

“…Population controls were 487 anonymous volunteers who also had been ascertained at the Hannover Medical School. These series had been used previously to determine the frequency of common mutations in the BRCA1 and ATM genes 19,20 as well as the frequency of the 1100delC mutation of the CHEK2 gene.10 Byelorussian cases were 424 breast cancer patients who had been diagnosed during the years 1998-2003 at the Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N. (n 5 70) or at one of the regional oncology centers in Gomel (n 5 94), Mogilev (n 5 107), Grodno (n 5 58), Brest (n 5 46) or Vitebsk (n 5 49).…”

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confidence: 99%

Association of two mutations in the CHEK2 gene with breast cancer

Bogdanova

Enssen-Dubrowinskaja

Feshchenko³

et al. 2005

Intl Journal of Cancer

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The 1100delC mutation of the cell cycle checkpoint kinase 2 (CHEK2) gene confers an increased risk for breast cancer, but the clinical impact of other CHEK2 gene variants remains unclear. We determined the frequency of two functionally relevant CHEK2 gene mutations, I157T and IVS211G > A, in two large series of breast cancer cases and controls from two independent populations. Our first series consisted of a hospital-based cohort of 996 German breast cancer cases and 486 population controls, and the second series consisted of 424 breast cancer patients and 307 population controls from the Republic of Belarus. The missense substitution I157T was identified in 22⁄996 cases (2.2%) vs. 3⁄486 controls (0.6%; OR 5 3.6, 95% CI 1.1-12.2, p 5 0.044) in the German population and in 24⁄424 cases (5.7%) vs. 4⁄307 controls (1.3%; OR 5 4.5, 95% CI 1.6-13.2, p 5 0.005) in the Byelorussian cohorts. The splicing mutation IVS211G > A was infrequent in both populations, being observed in 3⁄996 German and 4⁄424 Byelorussian patients (0.3% and 0.9%, respectively) and in 1⁄486 German controls (0.2%; adjusted OR 5 4.0, 95% CI 0.5-30.8, p 5 0.273). Heterozygous CHEK2 mutation carriers tended to be diagnosed at an earlier age in both populations, but these differences did not reach statistical significance. Family history of breast cancer did not differ between carriers and noncarriers. Our data indicate that the I157T allele, and possibly the IVS211G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility. ' 2005 Wiley-Liss, Inc.Key words: breast cancer; CHEK2; Germany; Belarus Cell-cycle checkpoint kinase 2 (CHEK2) is a central mediator of cellular responses to DNA damage.1,2 Ionizing radiation activates the CHEK2 protein via ATM-mediated phosphorylation, 3,4 and activated CHEK2 kinase can phosphorylate several substrates, including Cdc25A, p53 and E2F1, which mediate cell cycle arrest and apoptosis.1,2,5 CHEK2 phosphorylation of the breast cancer susceptibility protein BRCA1 regulates DNA double-strand break repair, 6 and deletion of CHEK2 potentiates the incidence of mammary carcinomas in BRCA1 conditional mutant mice.7 A truncating variant of CHEK2, the 1100delC mutation, has been identified as a low-penetrance breast-cancer susceptibility allele. 8,9 Heterozygous 1100delC carriers have an approximately 2-fold increased risk for breast cancer.10 Furthermore, a potential association of the 1100delC mutation with colorectal and prostate cancers has been reported. 11-13The role of variants in CHEK2 other than 1100delC is less clear. Most studies have led to the conclusion that other CHEK2 mutations do not make a major contribution to breast cancer susceptibility.14-16 However, one more recent investigation suggests that the common I157T mutation may be associated with increased breast cancer risk. 17 Parallel work has provided evidence that the missense substitution I157T as well as the splicing mutation IVS211G>A may confer an elevated risk for prostate cancer. 13,18 To assess the role of these CHEK2 varia...

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“…BRCA1 mutations previously found in neighboring countries such as Austria (2795del4bp) 31 and The Netherlands (2804delAA and IVS21-35del510bp) 10,32 were also identified in our breast cancer population. Common mutations in the German patient group include sequence changes such as 5382insC 33 and 300T3 G that have been found frequently in multiple, apparently diverse populations. 34 Indeed, both mutations account for almost 30% of deleterious BRCA1 alleles in our population.…”

Section: Mutation Spectrum For German Breast/ovarian Cancer Familiesmentioning

confidence: 99%

Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

2001

Intl Journal of Cancer

193

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The main focus of this German-wide multi-center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than 1 ⁄3 of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure.

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Frequency of BRCA1 Mutation 5382insC in German Breast Cancer Patients

Cited by 67 publications

References 9 publications

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Association of two mutations in the CHEK2 gene with breast cancer

Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

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