Territorial manifestation features of multiple primary malignant neoplasms in carriers of germline mutations in the BRCA 1 gene in Republic of Bashkortostan.
Authors: Sultanbaev Alexnder Valerievich , Menshikov Konstantin , Musin Shamil , Nasretdinov Ainur , Sultanbaeva Nadezda , Menshikova Irina , Lipatov Oleg , Izmailov Adel , Ayupov Rustem , Serebrennikov Grigoriy , Lipatov Danila 
Published: June 2022

e22523

Background: Recent advances in the diagnostic and therapeutic fields of oncology have increased the life expectancy of cancer patients, and therefore carriers of germline mutations, who are at high risk of developing a malignant neoplasm, also have a higher risk of developing a second synchronous or metachronous malignant tumor. The aim of this work is to study the features of the development of primary multiple malignant neoplasms in patients with germline mutations in the repair genes. Methods: Among all treated in the Republican Clinical Oncological Dispensary patients germline mutations in the repair genes were detected in 225 persons. Mutations were determined by polymerase chain reaction (PCR). The material of the study was a sample of venous blood taken from a patient on an empty stomach. A diagnostic panel was used to detect the most common mutations in Russia in the BRCA1 (5382insC, 4153delA, 300T > G, 185delAG, 2080delA, 3819delGTAAA) and BRCA2 (6174delT) genes. In the absence of a mutation, the study was carried out by the next generation sequencing (NGS) method. Results: After a molecular genetic study from 2014 to 2021, we determined the spectrum of germline mutations in residents of the Republic of Bashkortostan: BRCA 1 - c.5266dupC, c.3143delG, c.5161C > T, c.5382 insC, c.3819delGTAAA, c. 300T > G, c.5136G > A, 185delAG, 4153delA, 2080delA; BRCA 2 - c.6621_6622del, p.39-1_39delGA, c.961_962insAA. Among carriers of germinal mutations, primary multiple cancer was registered in 14.6% (33/225) of patients with mutations in the BRCA 1 genes. The following mutations were identified in patients with primary multiple malignant neoplasms: c.5382 insC and c.3819delGTAAA in the BRCA gene 1. The first primary breast cancer was registered in 10.6% (24/225) of patients, ovarian cancer in 1.8% (4/225), gastric cancer in 0.4% (1/225), primary multiple synchronous breast and ovarian cancer in 1.8% (4/225). In carriers of germinal mutations, manifestations of the first primary cancer were observed at the age of 29 to 60 years. The manifestation of the second primary cancer was registered in 2-18 years after the manifestation of the first primary cancer. Twenty-two patients subsequently developed a second primary breast cancer and 11 patients developed ovarian cancer. Also, 6 patients had a manifestation of the third primary cancer of the breast, ovaries or stomach in 8-26 years after the manifestation of the second primary cancer. Conclusions: Primary multiple cancer in carriers of germline mutations in the Republic of Bashkortostan was observed in 14.6% (33/225) of patients with mutations in the BRCA 1 genes. The period of manifestation of a secondary malignant tumor ranged from 2 to 18 years. This study plays an important role in the process of optimizing screening for multiple primary malignant neoplasms for carriers of germline mutations.