Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer patients

Dodova, R.; Mitkova, A.; Dacheva, Daniela; Hadjo, Lina Basam; Vlahova, A.; Hadjieva, Margarita Stoyanova Taushanova; Valev, Spartak; Caulevska, Marija Mitko; Popova, Stanislava; Popov, Ivan; Dikov, Tihomir; Sedloev, Theophil; Ionkov, A; Timcheva, K.; Christova, S.; Kremensky, Ivo; Mitev, Vanio; Kaneva, Radka

doi:10.1186/s12885-015-1516-2

Cited by 20 publications

(22 citation statements)

References 34 publications

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“…The age characteristic of patients who have breast cancer in the present study, revealed that the highest frequency of breast cancer patients among (40-50) years old (40%), followed by the age group of ( 30-39) years old (20%) , and the less frequency in the age (19-29) years (10%) , which has no signi icant differences as compared with control group (p > 0.05) mean 46.38 years (SD14.34) , so breast cancer is a disease of all ages, considering the entire lifespan (Walters, 2004). The results of our present study are agreed with (Walters, 2004) since the results of their study which included 200 Bulgarian females with breast cancer (postoperative and the age ranged from 25 to74 years) selected by the established genetic testing criteria, the mean age of the patients at diagnosis was 49.5 years , and no signi icant association between patients group and controls group (p > 0.05) (Dodova and Ivanova, 2015). So our indings are comparable with a study conducted an average 12% of women worldwide related breast cancer, their ages ranged between <40 ->70 years and showed 48.5 years mean of patients ages (Mcguire, 2015).…”

Section: -Demographic Characteristicssupporting

confidence: 92%

Molecular study of BRCA-1,2 and P53 gene polymorphisms among post-operative breast cancer patients

Al-salin

Al-Hilaly

Magid

2019

ijrps

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Breast cancer is a malignant tumor in groups of cancer cells that may develop into (invade) or spread to distant body regions around tissues. In both advanced and developing nations and in many parts of the globe, the burden of breast cancer is rising. It's the most prevalent malicious person illness in females, with 18% of all female cancers and the third most prevalent cause of cancer death globally. This case-control study was organized to explore the potential role of chosen genetic parameters in the Al-Diwanyia province in random samples of breast cancer patients the research, 5 ml of blood samples from 50 women with post-operative breast cancer attending the outpatient oncology department at Al Diwaniyia Teaching Hospital were employed compared to 50 women without cancer, patient ages and control ranged from 18 to 80 years. Among the three susceptibility genes studied, BRCA In BRCA-1 GG genotype evidently proposed a risk factor for tumor as had an (OR 5.3191) and risk factor (EF 0.065); AG & AA genotypes, on the other hand, played a rather preventive part as they had no risk factor (PF) of 0.0476 & 0.1667 respectively and low OR (0.7619 & 0.7917 respectively) and patients had 16%, and 84% of patients had G and A alleles respectively. The genotype of BRCA-2 AG As had the risk factor (OR 13.4146) and the risk factor (EF 0.1851), the AA genotype, on the other hand, did not have a risk factor role since it had a protective fraction (PF) of 0.9103 and a low OR (0.0731). Patients have 10% of G and 90% of A alleles compared to 100% of A only. In the P53 CC genotype, tumor etiology has evidently been proposed, as was the case with (OR 1.2941) and risk factor (EF 0.091). The GC genotype, on the other hand, did not have a risk factor as it had (PF) of 0.087 and low OR (0.4565) and patients had 56 percent of G allele and 44 percent of C allele compared to 52 percent of G and 48 percent of C control.

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Section: -Demographic Characteristicssupporting

confidence: 92%

Molecular study of BRCA-1,2 and P53 gene polymorphisms among post-operative breast cancer patients

Al-salin

Al-Hilaly

Magid

2019

ijrps

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“…The amount of rare mutations found in our study may be similar in other countries assumed to have a strong founder effect. In a recent study from Bulgaria, 200 individuals from breast/ovarian cancer families were genotyped with sequencing, and comparable results were found [ 24 ]. Two new, and five previously known mutations were identified in BRCA2 , while two new and six previously known mutations were identified in BRCA1 .…”

Section: Discussionmentioning

confidence: 73%

BRCA1 and BRCA2 mutation spectrum – an update on mutation distribution in a large cancer genetics clinic in Norway

Heramb

Wangensteen

Grindedal

et al. 2018

Hered Cancer Clin Pract

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BackgroundFounder mutations in the two breast cancer genes, BRCA1 and BRCA2, have been described in many populations, among these are Ashkenazi-Jewish, Polish, Norwegian and Icelandic. Founder mutation testing in patients with relevant ancestry has been a cost-efficient approach in such populations. Four Norwegian BRCA1 founder mutations were defined by haplotyping in 2001, and accounted for 68% of BRCA1 mutation carriers at the time. After 15 more years of genetic testing, updated knowledge on the mutation spectrum of both BRCA1 and BRCA2 in Norway is needed. In this study, we aim at describing the mutation spectrum and frequencies in the BRCA1/2 carrier population of the largest clinic of hereditary cancer in Norway.MethodsA total of 2430 BRCA1 carriers from 669 different families, and 1092 BRCA2 carriers from 312 different families were included in a quality of care study. All variants were evaluated regarding pathogenicity following ACMG/ENIGMA criteria. The variants were assessed in AlaMut and supplementary databases to determine whether they were known to be founder mutations in other populations.ResultsThere were 120 different BRCA1 and 87 different BRCA2 variants among the mutation carriers. Forty-six per cent of the registered BRCA1/2 families (454/981) had a previously reported Norwegian founder mutation. The majority of BRCA1/2 mutations (71%) were rare, each found in only one or two families. Fifteen per cent of BRCA1 families and 25% of BRCA2 families had one of these rare variants. The four well-known Norwegian BRCA1 founder mutations previously confirmed through haplotyping were still the four most frequent mutations in BRCA1 carriers, but the proportion of BRCA1 mutation carriers accounted for by these mutations had fallen from 68 to 52%, and hence the founder effect was weaker than previously described.ConclusionsThe spectrum of BRCA1 and BRCA2 mutations in the carrier population at Norway’s largest cancer genetics clinic is diverse, and with a weaker founder effect than previously described. As a consequence, retesting the families that previously have been tested with specific tests/founder mutation tests should be a prioritised strategy to find more mutation positive families and possibly prevent cancer in healthy relatives.

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“…However, controversial reports exist about the role of SNPs in these BRCA1/2 genes for the induction of human breast and ovarian cancer (HBOC). 2 , 18 , 21 , 22 , 23 Dombernowsky et al 22 reported that missense mutations cannot explain the risk of HBOC in women with familial history. Contrarily, Dodova et al 21 in their study implicated the role of missense variants which may be deleterious.…”

Section: Discussionmentioning

confidence: 99%

“… 2 , 18 , 21 , 22 , 23 Dombernowsky et al 22 reported that missense mutations cannot explain the risk of HBOC in women with familial history. Contrarily, Dodova et al 21 in their study implicated the role of missense variants which may be deleterious. In an Iranian population, Neamatzadeh et al 23 detected these polymorphic SNPs at higher frequency in BRCA1 and BRCA2 genes compared to control subjects supporting our data.…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients

Shah¹,

Shah²,

Panchal³

et al. 2018

TACG

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BackgroundGermline mutations BRCA1 and BRCA2 contribute almost equally in the causation of breast cancer (BC). The type of mutations in the Indian population that cause this condition is largely unknown.PurposeIn this cohort, 79 randomized BC patients were screened for various types of BRCA1 and BRCA2 mutations including frameshift, nonsense, missense, in-frame and splice site types.Materials and methodsThe purified extracted DNA of each referral patient was subjected to Sanger gene sequencing using Codon Code Analyzer and Mutation Surveyor and next-generation sequencing (NGS) methods with Ion torrent software, after appropriate care.ResultsThe data revealed that 35 cases were positive for BRCA1 or BRCA2 (35/79: 44.3%). BRCA2 mutations were higher (52.4%) than BRCA1 mutations (47.6%). Five novel mutations detected in this study were p.pro163 frameshift, p.asn997 frameshift, p.ser148 frameshift and two splice site single-nucleotide polymorphisms (SNPs). Additionally, four nonsense and one in-frame deletion were identified, which all seemed to be pathogenic. Polymorphic SNPs contributed the highest percentage of mutations (72/82: 87.8%) and contributed to pathogenic, likely pathogenic, likely benign, benign and variant of unknown significance (VUS). Young age groups (20–60 years) had a high frequency of germline mutations (62/82;75.6%) in the Indian population.ConclusionThis study suggested that polymorphic SNPs contributed a high percentage of mutations along with five novel types. Younger age groups are prone to having BC with a higher mutational rate. Furthermore, the SNPs detected in exons 10, 11 and 16 of BRCA1 and BRCA2 were higher than those in other exons 2, 3 and 9 polymorphic sites in two germline genes. These may be contributory for BC although missense types are known to be susceptible for cancer depending on the type of amino acid replaced in the protein and associated with pathologic events. Accordingly, appropriate counseling and treatment may be suggested.

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Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer patients

Cited by 20 publications

References 34 publications

Molecular study of BRCA-1,2 and P53 gene polymorphisms among post-operative breast cancer patients

Molecular study of BRCA-1,2 and P53 gene polymorphisms among post-operative breast cancer patients

BRCA1 and BRCA2 mutation spectrum – an update on mutation distribution in a large cancer genetics clinic in Norway

Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients

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