Abstract 43: Distribution and frequency of BRCA gene mutations in Turkish population including Balkan Turks
Authors: Akdeniz Demet , Tuncer Bugra S. , Kilic Seda , Sukruoglu Ozge , Kilic Leyla , Altundag Kevser , Ciftci Rumeysa , Ozel Sevda , Karabulut Senem , Ekenel Meltem , Saip Pinar , Karanlik Hasan , Cabioglu Neslihan , Yazici Hulya 
Published: May 2015

Abstract
Background: The distribution of hereditary breast and ovarian cancer in Turkish population has been reported in earlier publications. However, the regional distributions of breast cancer and/or BRCA1/2 gene mutations frequency are not known for Balkan Turks who came to Turkey for the forced migration in 1989 and for general Turkish populations in Turkey.
Materials and Method: We recruited 401 patients with a family history of breast and/or ovarian cancers, and 126 early-onset breast cancer cases below age 40 with/without a family history of cancer between 1994-2013. These patients were referred to Cancer Genetics Department of Oncology Institute in University of Istanbul. Families were selected from consecutive referrals to the above-listed hospital meeting specific family-history criteria (either multiple cases of breast and or ovarian cancer in the family or the presence of an individual with a young age at diagnosis). Mean age of patients in the study was 41, 18±10, 24.
Results: The distributions of patients participating in the study were evaluated in total 8 groups such as seven geographic regions of Turkey and the Balkan Turks. Overall frequency of BRCA1/2 gene mutations in Turkish population was 10%. The distribution of patients according to 8 groups were 26.6% in the Black Sea Region, 21.5% in the Marmara Region, 17.6% in the Eastern Anatolia Region, 8.6% in Central Anatolia, 3.1% in Aegean Region, 3.9% in the Mediterranean region, 2.7% in South Eastern Anatolia and 16% in Balkan Turks. BRCA1 and BRCA2 positivity was evaluated in the study groups: BRCA1/2 mutations ratio were 20% in the Black Sea Region, 16% in the Marmara Region, 20% in the Eastern Anatolia Region, 12% in Central Anatolia, % 4 in Aegean Region and 28% in the Balkan Turks. None of mutations in both genes were found in the patients participating in the study from South Eastern Anatolia and the Mediterranean regions. The observed BRCA1/2 mutations rate was found almost two-fold according to the expected mutation rate in the group of Balkan Turks. The highest breast cancer rates were seen in the city of Giresun in the Black Sea Region and in the city of Malatya in the Eastern Anatolia Region, respectively.
Conclusions: In our study, breast cancer was more frequent in the regions which were the Black Sea, the Marmara, Eastern Anatolia and the Balkan Turks group. Although the Marmara region was industrialized, Bulgaria where Balkan Turks lived before forced-migration and the Black Sea Region are not industrialized areas. However, in 1986, these regions were the most affected by the Chernobyl disaster and these interactions was described with scientific data. Therefore, it might be concluded that the high rates of breast cancer are associated with the Chernobyl disaster in these regions.
In the study, BRCA1/2 gene mutation rates were examined in Balkan Turks who came to Turkey by forced-migration after Chernobyl disaster. In the group of Balkan Turks, almost two fold expected incidence for BRCA1/2 gene mutations was observed. The investigated society was a small community living as a minority in Bulgaria. Therefore, it was suggested that the society was isolated as a nature and has been had high BRCA1/2 mutations rate.
On the other hand, in the study, BRCA1/2 gene mutations and clinical/pathological data were also compared and survival analysis was performed in the general Turkish population. The diagnosis age for breast cancer was found 10 years earlier when compared to the other populations (p&lt;0,005). BRCA1/2 mutations were not shown in the patients below age of 30. High frequency of the BRCA1 positivity was observed in triple negative patients (P &lt;0.05).
Citation Format: Demet Akdeniz, Bugra S. Tuncer, Seda Kilic, Ozge Sukruoglu, Leyla Kilic, Kevser Altundag, Rumeysa Ciftci, Sevda Ozel, Senem Karabulut, Meltem Ekenel, Pinar Saip, Hasan Karanlik, Neslihan Cabioglu, Hulya Yazici. Distribution and frequency of BRCA gene mutations in Turkish population including Balkan Turks. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 43. doi:10.1158/1538-7445.CANSUSC14-43