High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

Suspitsin, Evgeny N.; Sherina, Natalia; Ponomariova, Daria N.; Sokolenko, Anna P.; Iyevleva, Aglaya G.; Gorodnova, Tatyana; Zaitseva, Olga A.; Yatsuk, Olga S.; Togo, Alexandr V.; Tkachenko, Nathalia N.; Shiyanov, Grigory A; Lobeiko, Oksana S; Krylova, Nadezhda Yu; Matsko, Dmitry E.; Maximov, S.; Urmancheyeva, Adel F; Porhanova, N V; Imyanitov, Evgeny N.

doi:10.1186/1897-4287-7-5

Cited by 35 publications

(28 citation statements)

References 46 publications

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“…This founder mutation has been reported in 70 to 90% of Jewish families with high risk of breast and ovarian cancer [14]. The highest prevalence of this BRCA1 mutation has been observed in Eastern European countries (reaching 30 to 40%) such as Poland [15], Russia [16], Hungary [17] and Greece [18]. Less prevalence has been seen in Germany [19] and Italy [20] but it has not been found in Spanish population [21] nor in Moroccan [22] and Algerian populations [23].…”

Section: Discussionmentioning

confidence: 97%

Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer

et al. 2014

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Section: Discussionmentioning

confidence: 97%

Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer

et al. 2014

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“…Nevertheless, the meta-analyses published by Weischer et al (2008) showed that CHEK2 1100delC is an important breast cancer predisposition factor, increasing the risk by three-to five-fold. Studies carried out in Poland and neighboring countries shows that this mutation occurred in 0.0-5.2% breast cancer patients versus 0.0-0.92% in controls (Dufault et al 2004;Kleibl et al 2005;Rashid et al 2005;Kwiatkowska et al 2006;Cybulski et al 2007a;Fedorova et al 2007;Sokolenko et al 2007;Suspitsin et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Irrelevance of CHEK2 variants to diagnosis of breast/ovarian cancer predisposition in Polish cohort

et al. 2010

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CHEK2 gen encodes cell cycle checkpoint kinase 2 that participates in the DNA repair pathway, cell cycle regulation and apoptosis. Mutations in CHEK2 gene may result in kinase inactivation or reduce both catalytic activity and capability of binding other proteins. Some studies indicate that alterations in CHEK2 gene confers increase the risk of breast cancer and some other malignancies, while the results of other studies are inconclusive. Thus the significance of CHEK2 mutations in aetiology of breast cancer is still debatable. The aim of our study was to evaluate the relationship between the breast/ovarian cancer and CHEK2 variants by: i) the analysis of the frequency of selected CHEK2 variants in breast and ovarian cancer patients compared to the controls; ii) evaluation of relationships between the certain CHEK2 variants and clinico-histopathological and pedigree data. The study was performed on 284 breast cancer patients, 113 ovarian cancer patients and 287 healthy women. We revealed the presence of 430T > C, del5395 and IVS2 + 1G > A variants but not 1100delC in individuals from both study and control groups. We did not observe significant differences between cancer patients and controls neither in regard to the frequency nor to the type of CHEK2 variants. We discussed the potential application of CHEK2 variants in the evaluation of breast and ovarian cancer predisposition.

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“…BRCA1/2 testing was initiated at the N.N. Petrov Institute of Oncology (St Petersburg, Russia) in 2007 as part of research activities 9. All ovarian cancer patients were tested for recurrent Slavic mutations 10.…”

Section: Methodsmentioning

confidence: 99%

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

Gorodnova

Sokolenko

et al. 2019

Int J Gynecol Cancer

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ObjectiveTumors arising in BRCA1/2 mutation carriers are characterized by increased platinum sensitivity; however, it is unknown whether this feature should be considered while choosing between primary surgical versus systemic treatment. This study aimed to compare outcomes of ovarian cancer patients undergoing either primary surgery or interval cytoreduction based on BRCA1/2 status.MethodsThe study included consecutive ovarian cancer patients, who were treated at the N.N. Petrov Institute of Oncology (St Petersburg, Russia) from 2000 to 2013 and who underwent complete or optimal cytoreductive surgery. A comparison of disease outcomes was performed for the total group of ovarian cancer patients as well as for 69 BRCA1-mutated and 151 sporadic high-grade serous advanced-stage ovarian carcinomas. Frequency comparisons were performed by Chi-square test or Fisher exact test. Disease-free interval and overall survival were analyzed by Mann-Whitney U-test and Kaplan-Meier method. Hazard ratios were calculated by Cox regression analysis.ResultsThe analysis included 283 consecutive patients who underwent optimal cytoreduction (size of residual tumor <1 cm (n=156)) or complete tumor excision (n=127) on primary surgery (n=168) or after neoadjuvant chemotherapy (n=115). 84 patients carried germline mutation in BRCA1 (n=77) or BRCA2 (n=7) genes, while 199 ovarian cancer patients were classified as sporadic. High-grade serous ovarian cancer patients treated with neoadjuvant chemotherapy had a lower disease-free interval compared with those undergoing primary surgery followed by adjuvant therapy (7.8 vs 14.2 months, p<0.001). This difference was attributed mainly to sporadic cases (5.1 vs 12.2 months, p<0.001), while BRCA1-associated cancers had a similar disease-free interval regardless of the sequence of treatments (12.5 vs 15.8 months, p=0.53). When treated with neoadjuvant chemotherapy, BRCA1-mutated patients had improved overall survival as compared with sporadic cases (45.7 vs 25.3 months, p=0.007), while patients subjected to primary surgery showed similar overall survival irrespective of BRCA1 status (54.6 vs 53.9 months, p=0.56). A total of 29/61 (48%) BRCA1/2-associated patients relapsed as a single local tumor; this was lower in sporadic cancer patients (38/134 (28%); p=0.01).ConclusionIn BRCA1 mutation carriers, the oncologic outcomes are similar when comparing primary surgery versus neoadjuvant chemotherapy. In addition, BRCA1-mutation carriers often have a single site of disease when diagnosed with recurrent ovarian cancer.

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High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

Cited by 35 publications

References 46 publications

Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer

Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer

Irrelevance of CHEK2 variants to diagnosis of breast/ovarian cancer predisposition in Polish cohort

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

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