Алельний поліморфізм гена TOX3/LOC643714 у хворих на рак молочної залози без впливу іонізуючого випромінювання в анамнезі

Abstract

Метою роботи було встановлення взаємозв’язку поліморфізму rs 3803662 гена TOX3/LOC643714 з ризиком розвитку раку молочної залози (РМЗ) у хворих без впливу іонізуючого випромінювання (ІВ) в анамнезі. Визначення поліморфізму rs 3803662 гена TOX3/LOC643714 проводилося шляхом ПЛР у 41 хворої на рак молочної залози без впливу ІВ в анамнезі. В групі хворих на РМЗ без впливу ІВ в анамнезі розподіл генотипів вірогідно відповідав рівнянню Харді-Вайнберга. Не було виявлено асоціації поліморфізму rs 3803662 гена TOX3/LOC643714 з ризиком розвитку спонтанного раку молочної залози у групі хворих РМЗ. Отримані результати по розподілу частот генотипів поліморфізму rs 3803662 гена TOX3/LOC643714 у групі хворих на рак молочної залози співпадають із даними літератури по розподілу частот генотипів поліморфізму rs 3803662 гена TOX3/LOC643714 у російській популяції, з якими було проведено порівняння.

Целью работы было установление взаимосвязи полиморфизма rs 3803662 гена TOX3/LOC643714 с риском развития рака молочной железы (РМЖ) у больных без влияния ионизирующего излучения в анамнезе. Определение полиморфизма rs 3803662 гена TOX3/LOC643714 проводилось путем ПЦР у 41 больного раком молочной железы без влияния ионизирующего излучения в анамнезе. В группе больных РМЖ без влияния ионизирующего излучения в анамнезе распределение генотипов достоверно отвечало уравнению Харди-Вайнберга. Не было выявлено ассоциации полиморфизма rs 3803662 гена TOX3/LOC643714 с риском развития спонтанного рака молочной железы в группе больных РМЖ. Полученные результаты по распределению частот генотипов полиморфизма rs 3803662 гена TOX3/LOC643714 в группе больных раком молочной железы совпадают с данными литературы по распределению частот генотипов полиморфизма rs 3803662 гена TOX3/LOC643714 в российской популяции, с которыми было проведено сравнение.

Breast cancer (BC) is the most commonly diagnosed cancer and the most common cause of cancer deaths among women throughout the world. It is well known that breast cancer is a heterogeneous disease not only in the aspect of different pathogenesis, but also in relation to clinical manifestations and treatment outcomes. Data from epidemiological studies confirmed the existence of a causal relationship between the development of breast cancer and the effect of ionizing radiation. In addition, the probability of increasing the risk of developing radiation cancer in the presence of a genetically predisposed predisposition to its occurrence is discussed. Developmental radiation can be promoted by low-penetrance genes whose polymorphism is common in the general population. To test the hypothesis, several large-scale studies have been planned and conducted by many collectives of scientists from Western, Eastern Europe, USA and Asia, which studied breast cancer associations with different genomic variations (Genome-Wide Association Studies – GWAS). In these works, hundreds of thousands of singlenucleotide polymorphisms (SNPs) have been investigated and their association with breast cancer has been established in several thousand patients. The polymorphisms rs2981582, rs1219648, rs1078806 of the FGFR2 gene; rs3803662, rs12443621 of the TNRC9/TOX3 gene, 16q12.1; rs889312 of MAP3K1 gene, 5q11.2 and rs3817198 of the LSP1 gene is associated with the risk of developing breast cancer. Locus TOX3/LOC643714 has chromosome 16 being one of the first sites identified by a genetic study of populations of European and Asian origin. Of the multiple SNPs associated with the risk of developing breast cancer, rs3803662 (change in C to T) was most strongly associated with the disease, each copy of the T rs3803662 allele was associated with a 20% increase in risk of developing a breast cancer. Further studies, including analysis of European-derived populations, showed that the risk caused by rs3803662 polymorphism was or was limited to tumors with positive ER status (estrogen receptor) or had stronger association with them than receptor-negative tumors. Due to the fact that most of the studies were conducted among populations of European origin, it is not known whether it is associated with the risk of developing the same SNP in the population of the African descent. In the subgroup of African-American women (422 patients and 447 representatives of the control group) in the study. The aim was to establish the relationship of gene polymorphism rs 3803662 in TOX3/LOC643714 with developing breast cancer in patients without ionizing radiation in history. Identifying rs 3803662 polymorphism in TOX3/LOC643714 gene was conducted by PCR in 41 patients with breast cancer with no ionizing radiation (IR) in previous history. In patients with breast cancer without affecting the IR history distribution of genotypes was likely to meet Hardy-Weinberg equation. There was no association of rs 3803662 polymorphism of TOX3/LOC643714 gene with the risk of spontaneous breast cancer in patients with breast cancer. The results for the distribution of genotype frequencies in rs 3803662 polymorphism of TOX3/LOC643714 gene in patients with breast cancer are consistent with the literature on the frequency distribution of genotypes in rs 3803662 polymorphism of TOX3/LOC643714 gene in Russian population, with which the comparison was made.