Polymorphisms of MicroRNA and ESR1 Genes and Their Association with Triple Negative Breast Cancer Risk and Prognosis
|School||Beijing Union Medical College|
|Keywords||Triple negative breast cancer miRNA ESR1 Genetic polymorphism Cancer susceptibility Prognosis|
Background and purpose: triple negative breast cancer (with TNBC) is more common, but treatment is limited, a special type of tumor with poor prognosis, is also a class of multi-gene genetic diseases. Small molecule RNA (microRNA, miRNA) is an important molecules that regulate gene expression in a variety of tumor expression out of control, it may be one of the mechanisms promote tumor. Due to the miRNA genetic variation and ER, HER2 important receptor expression related to co-exist in the estrogen receptor alpha (ESR1) gene single nucleotide polymorphism (SNP) sites are possible in the occurrence and development of TNBC from important role, therefore, this study explores the Chinese Han population exists in the sequence of miRNA genes and regulation of breast cancer important receptor-associated SNP loci and ESR1 gene SNP loci TNBC sick relationship between risk and prognosis susceptible population screening can be used in order to find molecular markers, which provide the basis for clinical diagnosis and individualized treatment options. Methods: According to NCBI and public database information microRNA Base, known Han population miRNA minimum allele frequency (MAF) gt; 0.05 of SNP loci, the final selection of 23 sites of 22 miRNA genes in the mammary gland cancer cases (n = 384) and controls (n = 192) in the correlation analysis of the breast cancer susceptibility. On this basis, targeted research TNBC risk, focusing choose the regulation of ER, HER2 of miRNA gene SNP and exist in the ESR1 gene SNP loci, non-conditional logistic regression model to assess the sites TNBC risk associated with TNBC prognosis and Kaplan-Meier analysis. Finally admitted to our hospital from January 1999 to December 2007 134 patients with advanced TNBC patients clinical data, retrospective study of the clinical features, the living conditions and prognostic factors, and further analysis of the ESR1 gene polymorphic loci and late TNBC prognosis. Results: In this study, 22 miRNA genes 23 SNP loci between the risk of breast cancer, no significant correlation (P gt; 0.05). Association studies for the the TNBC incidence risk, we focus regulation of ER 4 SNP loci HER2 of miRNA genes and 4 of the ESR1 gene SNP loci results found to be in possession of the ESR1 rs3798759-GG genotype of the population suffering from TNBC a reduced risk (OR = 0.8015,95% CI = 0.4206-1.5272, p = 0.0239), prompted carry ESR1 rs3798759-GG genotype possible protective factors TNBC illness. Ⅰ, Ⅱ stage TNBC patients carrying the rs3798759-G allele in patients with 5-year DFS (41.9%) was significantly lower than the carrying rs3798759-T allele patients (55.8%) (P = 0.032); year OS (82.6%) is also lower than the carrying rs3798759-T allele patients (94.1%), but the P value has not yet reached a statistically significant difference in the level (P = 0.082). These results suggest that in Ⅰ, Ⅱ stage TNBC, carrying the rs3798759-G allele in patients with a poor prognosis. Finally, late with TNBC: analysis of clinical data, summarize TNBC recurrence transfer characteristics and the characteristics of the response to treatment and prognosis: the majority of patients (72.7%) were in the 2 years after surgery had local recurrence or distant at the transfer. The most common site of distant metastasis is the lung, 51.7% of patients at the same time the transfer of more than two parts. Late receiving first-line chemotherapy (P = 0.0001), as well as first-line chemotherapy patients (P = 0.0108), the median survival was significantly prolonged. COX proportional hazard model results show that, whether or not to accept the first-line chemotherapy as well as first-line chemotherapy efficacy late TNBC patients independent prognostic factors. In the late TNBC carry the ESR1 rs3798759-G allele eutopic OS of 37.6 months, significantly lower than patients carrying the rs3798759-T allele (75 months) (P = 0.019). Conclusion: SNP exists in the miRNA gene sequences and the Chinese mainland Han women between the risk of breast cancer found no significant correlation. ESR1rs3798759-GG genotype may be a Chinese female the TNBC prevalence of protective factors, and prognosis in TNBC Ⅰ, Ⅱ stage and late TNBC patients carrying the SNP loci show lower 5-year survival and The median survival time. There are complex interactions between environmental and genetic factors, each gene single nucleotide polymorphisms, and the limited number of cases of this study, therefore still a need for analysis and verification of large sample studies.