*112360*

Biological sciences / Genetics and cytology

RESEARCH FREQUENCY OF MUTATIONS IN BRCA1 OR BRCA2 IN PATIENTS WITH BREAST CANCER IN KABARDINO-BALKARIA.

PhD. Bogotova¹ Z.I., PhD. Bittueva¹ M.M., PhD. Mukov² M.B., PhD. Handohov¹ T.H., Dr. Kerefova M.K. zalina_bogotova@mail.ru

¹Kabardino-Balkarian State University. 360004, KBR, Nalchik, st. Chernyshevsky 173.

² “Cancer Clinic” Ministry of Health of the KBR. 360051, KBR, Nalchik, st. Lermontov, 23.

Key Words

Breast cancer, gene BRCA1, gene BRCA2, genetic predisposition, genotyping, PCR, Kabardino-Balkaria.

Abstract

Every year in the world registered 10 million new cancer cases and more than 6.2 million deaths from the disease in this group. 5 to 40% of malignant neoplasms of all anatomical locations have a hereditary etiology, and this percentage increases due to increased overall morbidity.

To date, the literature contains some 200 hereditary cancer syndromes, for 70 of which are fully transcribed primary molecular defects or chromosomal localization of the set of mutant genes, and DNA diagnostics has become a routine method of investigation in the course of verification of the genetic diagnosis.

These diseases include single-and double-sided breast cancer (BC). The subject of investigation in these cases are oncogenes and suppressor genes of malignant transformation of cells of BRCA1, BRCA2, CHEK2, TP53, MLH1 MSH2, conservative inherited defects that lead to the paradoxical risk of developing cancer, which reaches often 60-95%.

I. Introduction

Breast cancer (BC) is among the most common cancer among women. According to official figures "Cancer Clinic" Ministry of Health of the KBR in 2011 the total number of patients with this disease in Kabardino-Balkaria was more than 2000 people (an average of 54.1 cases per 100 thousand population).

The incidence of breast cancer contributes to the development of new approaches to diagnosis and treatment of precancerous conditions. The emergence of instrumental methods of examination of the female population has caused a significant increase in the number of diagnosed focal lesions of the mammary glands, and set the task of correctly interpreting the data obtained with their help. Hereditary breast cancer (BC) is the most common kind of family of tumors. His contribution to the overall incidence of breast cancer is approximately 5-10% [1].

The discovery of the gene BRCA1 (от Breast cancer - breast cancer), which in the case of mutations responsible for about half of all cases of hereditary breast cancer caused a great resonance in society and among researchers, oncologists [2].

Soon, to open the second gene responsible for predisposition to breast cancer, which was named BRCA2 [3]. In BRCA2, perhaps, lies the primary responsibility for the development of the majority of hereditary cases of the disease are not caused by the gene BRCA1. Women with mutations in the gene BRCA1 or BRCA2 breast cancer develops in 70-80% of cases with mutation of the BRCA1 gene associated high risk of developing ovarian cancer.

Successful treatment of the disease depends on the capabilities of its early diagnosis. In this regard, at the present time is particularly relevant to develop and implement effective methods of prediction and early diagnosis using molecular genetic technologies. Molecular-genetic approach is to identify mutations in repair genes that increase the risk of this disease. In a world of intense study the spectrum of mutations in the genes of a family of BRCA, which is specific to different populations. Knowledge of the mutation spectra characteristic of a country or region, allows using DNA diagnostics to identify groups at risk of developing the disease.

II. Statement of the problem

Russia has conducted a study on the spectrum of mutations in BRCA1 and BRCA2 genes in patients with familial forms of the disease, Moscow and Leningrad regions, and populations studied population of Bashkiria and the Chita region [4,5]. The leading position on the frequency of the mutation is 5382insC. These results are significant for practical DNA diagnosis of hereditary predisposition to breast cancer and ovarian cancer in Russia, mainly in women of Russian ethnic origin.

DNA extraction was performed using reagents "QIAamp DNA Blood Mini Kit" (firm «Qiagen»), for DNA amplification using a set of reagents for the detection of mutations in the genes BRCA1 and BRCA2, by allele-specific polymerase chain reaction. We investigated mutations 5382insC, 185delAG, 4154delA genes BRCA1 and 6174delT mutations in the gene BRCA2 (firm "Isogene", "Lytech").

III. Results

Similar studies conducted in the North Caucasus for the first time. Selection of patients with breast cancer (including questioning the nature of the disease) was held in conjunction with the staff of the dispensary. Material studies were blood samples of women with breast cancer (n = 100). The control group consists of women who are not clinically identified the disease (n = 110). The total number of the investigated sample - 210 people. The study refined data on the ethnicity of women through the survey and determine the nationality of the parents to the third generation. In the control and experimental group were three dominant nations residing in the territory of the Republic: Kabardian, Balkarian and Russian.

Among breast cancer cases were identified mutation carriers, and 5382insS 4154delA gene BRCA1, 6174delT BRCA2 gene in breast cancer patients, which suggests the establishment of hereditary forms of breast cancer that occurred against the backdrop of the "loss of heterozygosity."

IV. Conclusions

Comparison of allele frequencies of these susceptibility genes for hereditary breast cancer in the form of groups of patients and healthy women will identify genetic causes of cancer rates of growth, and to identify high-risk groups.

The outcome of the project among the studied contingent will be allocated a group of women who fall within the additional risk due to individual genetic variations. In addition, knowledge of the genetic status of the genes involved in carcinogenesis, except for the risk of the disease, will also personalize the prevention of disease.

ЛИТЕРАТУРА:

1. Имянитов Е.Н. Наследственный рак молочной железы// Практическая онкология. 2010 Т. 11. №4 C. 258-259.

2. Miki Y., Swensen J., Shattuck-Eidens D. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 // Science. 1994. V. 266. P. 66-71.

3. Easton D.F., Steele L., Fields P. et al. Cancer risks in two iarge breast cancer families linked to BRCA2 on chromosome 13q 12-13 // Am. J. Hum. Genet. 1995. V. 57. P. 1284-1297.

4. Тарасов В.А., Асланян М.М., Цырендоржиева Е.С., Литвинов С.С., Гарькавцева Р.Ф., Алтухов Ю.П. Генетически обусловленная подразделенность популяций человека по риску развития рака молочной железы у женщин // Доклады Академии наук. 2006. Т. 406. №2. С. 281-285.

5. Зинатуллина Г.З. Определение факторов прогноза течения рака молочной железы на основании молекулярно-генетичеких исследований: Автореф. дисс. на соискание уч.степени к.м.н. – Уфа, 2007.

References:

1. Imyanitov EN Hereditary breast cancer // Practical Oncology. 2010 T. 11. Number 4 C. 258-259.

2. Miki Y., Swensen J., Shattuck-Eidens D. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 // Science. In 1994. V. 266. P. 66-71.

3. Easton D.F., Steele L., Fields P. et al. Cancer risks in two iarge breast cancer families linked to BRCA2 on chromosome 13q 12-13 // Am. J. Hum. Genet. In 1995. V. 57. P. 1284-1297.

4. Tarasov, VA, Aslanian MM, Tsyrendorzhiyev ES, SS Litvinov, Garkavtseva RF, Altukhov JP Genetically caused by the subdivision of human populations at risk of developing breast cancer in women // Proceedings of the Academy of Sciences. In 2006. T. 406. Number 2. S. 281-285.

5. Zinatullina GZ Determining factors of prognosis of breast cancer based on molecular studies genetichekih: Abstract. thesis. for obtaining a PhD uch.stepeni - Ufa, 2007.