Анализ ассоциаций полиморфных вариантов генов hOGG1, APEX1, XPD, SOD2 и CAT, участвующих в процессах репарации ДНК и антиоксидантной защите, с риском развития рака молочной железы

Онкологические заболевания молочной железы – одна из ведущих причин смертности у женщин. Рак молочной железы относится к числу распространенных мультифакториальных полигенных заболеваний, реализующихся в результате сочетанного взаимодействия генетических и средовых факторов. Наиболее часто встречаются люминальные опухоли. Люминальный подтип В рака молочной железы характеризуется худшим прогнозом и ранними рецидивами. Для изучения генетических факторов риска развития злокачественных новообразований молочной железы необходимо определить полиморфные варианты генов, играющих важную роль в канцерогенезе, к числу которых относятся гены репарации ДНК и системы антиоксидантной защиты. Изучены ассоциации полиморфизмов генов hOGG1 (rs1052133), APEX1 (rs1130409), XPD (rs13181), SOD2 (rs4880) и CAT (rs1001179) у 313 некурящих пациенток в постменопаузе с диагнозом люминального подтипа В Her2-негативного рака молочной железы. В контрольную группу вошли 233 здоровые некурящие женщины в постменопаузе. Зарегистрированы с поправкой на возраст статистически значимые ассоциации полиморфных вариантов генов XPD (rs13181) и APEX1 (rs1130409) с риском развития люминального подтипа В Her2-негативного рака молочной железы в лог-аддитивной модели наследования, гена CAT (rs1001179) – в доминантной модели OR = 1.41; CI 95 %: 1.08–1.85; Padj = 0.011; OR = 1.39; CI 95 %: 1.07–1.81; Padj = 0.013 и OR = 1.70; CI 95 %: 1.19–2.43; Padj = 0.004 соответственно). В группе женщин пожилого возраста (60–74 года) выявлена ассоциация вариантов гена CAT (rs1001179) с риском развития рака молочной железы в лог-аддитивной модели наследования (OR = 1.87; CI 95 %: 1.22–2.85; Padj = 0.0024). С помощью MDR-анализа найдена наиболее оптимальная статистически значимая 3-локусная модель межгенных взаимодействий при развитии онкозаболеваний молочной железы люминального подтипа В. MDR-анализ показал также тесное взаимодействие и взаимное усиление эффектов между локусами APEX1 и SOD2 и независимость эффектов данных локусов от эффекта локуса САТ при формировании люминального подтипа В рака молочной железы.

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