Введение

tumors

Malignant tumours

2224-50572587-6813

Rosoncoweb

10.18027/2224-5057-2015-2-3-12

tumors-130

Research Article

ФУНДАМЕНТАЛЬНАЯ ОНКОЛОГИЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНА

FUNDAMENTAL ONCOLOGY AND EXPERIMENTAL MEDICINE

Однонуклеотидные полиморфизмы: роль в развитии рака молочной железы и перспективы клинического применения

Single nucleotide polymorphisms: the role of breast cancer development and clinical perspective

Батенева

Елена Ильинична

Bateneva

Elena Ilynichna

аспирант лаборатории клинической онкогенетики НИИ клинической онкологии;

н. с.,

Москва

PhD student of Laboratory of Clinical Oncogenetics;

researcher,

Moscow

elena.bateneva@gmail.com

Мещеряков

Андрей Альбертович

MESHCHERYAKOV

ANDREI

к. м.н., в. н.с. отделения химиотерапии и комбинированного лечения злокачественных опухолей НИИ клинической онкологии, Москва

Крохина

Ольга Владимировна

KROKHINA

OLGA

к. м.н., с. н.с. отделения реконструктивной и пластической онкологии НИИ клинической онкологии, Москва

Петровский

Александр Валерьевич

PETROVSKY

ALEXANDER

к. м.н., с. н.с. отделения радиохирургии, Москва

Рагимов

Алигейдар Агаалекпер оглы

RAGIMOV

ALIGEJDAR

д. м.н., профессор, заведующий кафедрой клинической трансфузиологии, Москва

Кадочникова

Владислава Викторовна

KADOCHNIKOVA

VLADISLAVA

к. б.н., с. н.с., Москва

Трофимов

Дмитрий Юрьевич

TROFIMOV

DMITRY

д. б.н., генеральный директор, Москва

Любченко

Людмила Николаевна

LYUBCHENKO

LYUDMILA

д. м.н., заведующая лабораторией клинической онкогенетики НИИ клинической онкологии, Москва

ФГБНУ «РОНЦ им. Н. Н. Блохина»; ЗАО «НПФ ДНК-Технология»РоссияFederal State Scientific Institution «Russian Cancer Research Center named after N. N. Blokhin”; LLC DNA-Technology,Russian Federation

ФГБНУ «РОНЦ им. Н. Н. Блохина»РоссияФГБНУ «РОНЦ им. Н. Н. Блохина»Russian Federation

Первый МГМУ им. И. М. СеченоваРоссияПервый МГМУ им. И. М. СеченоваRussian Federation

ЗАО «НПФ ДНК-Технология»РоссияЗАО «НПФ ДНК-Технология»Russian Federation

2015

01072015

02312

2015

Батенева Е.И., Мещеряков А.А., Крохина О.В., Петровский А.В., Рагимов А.А., Кадочникова В.В., Трофимов Д.Ю., Любченко Л.Н.

Bateneva E.I., MESHCHERYAKOV A., KROKHINA O., PETROVSKY A., RAGIMOV A., KADOCHNIKOVA V., TROFIMOV D., LYUBCHENKO L.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.malignanttumors.org/jour/article/view/130

Введение

Введение: Рак молочной железы – самое распространённое онкологическое заболевание у женщин во всём мире. Генетическая предрасположенность к раку молочной железы гетерогенна, обусловлена мутациями с высокой и средней пенетрантностью и однонуклеотидными полиморфизмами с низкой пенетрантностью. Точная оценка генетического риска позволит персонализировать программы профилактики и лечения, а также снизить смертность от рака молочной железы.

Задачи исследования

Задачи исследования: Определить частоты встречаемости однонуклеотидных полиморфизмов rs2981582 (FGFR2), rs3817198 (LSP1), rs889312 (5q11), rs13281615 (8q24), rs13387042 (2q35), rs3803662 (16q12) в неотобранной выборке больных раком молочной железы и у здоровых женщин в российской популяции, выявить возможные ассоциации указанных полиморфизмов с развитием рака молочной железы.

Материал и методы

Материал и методы: Обследованы неотобранные выборки больных раком молочной железы (963 человека), здоровых женщин-доноров крови (591 человек). Материалом служила цельная периферическая кровь, генотипирование проведено методом ПЦР в режиме реального времени с анализом кривых плавления с использованием оригинальных олигонуклеотидов.

Результаты

Результаты: Частоты минорных аллелей однонуклеотидных полиморфизмов составили 41,6±1,1% и 36,2±1,1% для rs2981582 (FGFR2), 35,3±1,1% и 34,3±1,1% для rs3817198 (LSP1), 39,3±1,1% и 43,7±1,1% для rs13387042 (2q35), 27,7±1,0% и 27,8±1,0% для rs889312 (5q11), 46,2±1,1% и 44,7±1,1% для rs13281615 (8q24), 35,7±1,1% и 29,9±1,1% для rs3803662 (16q12) в группах больных РМЖ и здоровых женщин, соответственно. Достоверные ассоциации с развитием рака молочной железы выявлены для полиморфизмов rs2981582 в гене FGFR2 (OR=1,26; 95% CI, 1,11–1,41; p=0,003), rs13387042 в локусе 2q35 (OR=0,84; 95% CI, 0,69–0,98; p=0,02) и rs3803662 в локусе 16q12 (OR=1,30; 95% CI, 1,14–1,45; p=0,002).

Выводы

Выводы: Подтверждён вклад прежде идентифицированных низкопенетрантных однонуклеотидных полиморфизмов rs2981582 в гене FGFR2, rs13387042 в локусе 2q35 и rs3803662 в локусе 16q12 в наследственную предрасположенность к раку молочной железы в российской популяции.

Background

Background. Breast cancer (BC) is the most prevalent cancer in women worldwide. Genetic susceptibility to BC is heterogeneous including mutations with medium to high penetrance and single nucleotide polymorphisms (SNPs) with low penetrance. Precise assessment of genetic risk would allow to personalize the programs of prevention and treatment of BC and to reduce mortality.

Objective

Objective. We aimed to determine the frequencies of single nucleotide polymorphisms rs2981582 (FGFR2), rs3817198 (LSP1), rs889312 (5q11), rs13281615 (8q24), rs13387042 (2q35), rs3803662 (16q12) in unselected group of BC patients and healthy women in Russian population, to reveal possible associations of these polymorphisms with BC development.

Subjects and methods

Subjects and methods. An unselected group of 963 patients with BC and control group of 591 healthy female blood donors were examined. Whole peripheral blood samples were used to extract genomic DNA. Real-time polymerase chain reaction with melting curves analysis was performed for SNP genotyping.

Results

Results: Minor allele frequencies were as follows: 41.6±1.1% and 36.2±1.1% for rs2981582 (FGFR2), 35.3±1.1% and 34.3±1.1% for rs3817198 (LSP1), 39.3±1.1% and 43.7±1.1% for rs13387042 (2q35), 27.7±1.0% and 27.8±1.0% for rs889312 (5q11), 46.2±1.1% and 44.7±1.1% for rs13281615 (8q24), 35.7±1.1% and 29.9±1.1% for rs3803662 (16q12) in group of BC patients and group of healthy women respectively. The obtained ORs for BC were 1.26 (95% CI, 1.11–1.41; p=0.003) for rs2981582, OR=0.84 (95% CI, 0.69–0.98; p=0.02) for rs13387042 and OR=1.30 (95% CI, 1.14–1.45; p=0.002) for rs3803662.

Conclusion

Conclusion: We confirmed the associations of previously identified SNPs rs2981582 (FGFR2), rs13387042 (2q35) and rs3803662 (16q12) with BC in Russian population.

рак молочной железынаследственная предрасположенностьоднонуклеотидный полиморфизм

breast cancergenetic predispositionsingle nucleotide polymorphism

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The authors declare that there are no conflicts of interest present.