Полиморфизмы генов TP53 (rs1042522) и MDM2 (rs2279744) в раке легкого: метаанализ

Рак легкого - один из наиболее распространенных видов рака в мире. Хотя механизм возникновения заболевания по-прежнему остается в значительной степени неизвестным, благодаря многочисленным исследованиям была выявлена связь между полиморфизмами генов и риском развития рака легкого. Решающую роль в поддержании стабильности генома и профилактике опухолей играет онкосупрессор р53. Ключевым регулятором белка р53 является MDM2. Несмотря на важность p53 сигнального пути в канцерогенезе, данные о вкладе SNP TP53 (rs1042522) и MDM2 (rs2279744) в развитие рака легкого очень противоречивы. Метаанализ, собирающий количественные данные из отдельных исследований и объединяющий их результаты, имеет преимущество, которое заключается в повышении точности, предоставлении надежных оценок и решении тех вопросов, когда исследование отдельных ассоциаций недостаточно эффективно. Целью нашей работы было изучение роли полиморфизмов ТP53 (rs1042522) и MDM2 (rs2279744) в формировании предрасположенности к раку легкого. Проведен метаанализ ассоциации полиморфизмов TP53 (rs1042522) и MDM2 (rs2279744) и рака легкого. В общей сложности рассмотрено 51 исследование типа «случай–контроль», включающее 25 366 пациентов с раком легкого и 25 239 здоровых индивидуумов. Результаты метаанализа показали отсутствие связи между раком легкого и MDM2 (rs2279744) во всех моделях. Примечательно, что ассоциация TP53 (rs1042522) с предрасположенностью к раку легкого наблюдалась в трех разных моделях (мультипликативная, аддитивная и доминантная). Стратификация по этническому признаку также указывает на связь между TP53 (rs1042522) и риском развития рака легкого как в азиатской, так и в европейской популяции. Проведенный метаанализ позволяет сделать вывод, что полиморфизм ТР53 (rs1042522), но не MDM2 (rs2279744), может обусловливать предрасположенность к раку легкого.

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