| Objective:To investigate the effect of long-chain non-coding RNA H19single nucleotide polymorphisms on the risk of breast cancer and the expression levels of plasma H19 mRNA,so as to further understand the pathogenesis of breast cancer which may providing a theoretical basis for early screening,diagnosis,prevention and molecular targeted therapy.Methods:From January 2015 to January 2016,228 patients were newly diagnosed with breast cancer in the Affiliated Hospital of Southwest Medical University.Before treated with surgery,radiotherapy or chemotherapy,the venous blood were drawed and collected.222 cases of healthy women were selected from the physical examination center as control group during the same period.H19 tag SNPs were searched and screened by bioinformatic software,4 SNP locus were finally identified and included:rs3741219,rs2107425,rs217727 and rs2839698.All tag SNPs were determined and genotyped by gene sequencing technologies.Hardy-Weinberg equilibrium of each SNP genotypes in healthy control group was tested to determine the population representation of the control group.The t-test and?~2 test were used to compare the general data,reproductive factors and family history of breast cancer between cases group and control group.The correlation between H19 SNP genotype and risk of breast cancer was analyzed by binary logistic regression analysis and stratification analysis.The expression levels of H19 mRNA in 90breast cancer patients with same clinical features were detected by qRT-PCR in order to investigate the effect of SNP genotype on H19mRNA expression.Western-Blot method was used to analyze the effect of H19 rs2839698 on EMT related protein Vimentin,and to further explore the specific mechanism of SNP in breast cancer.Results:There was no correlation between H19 rs3741219 and risk of breast cancer(P>0.05).CT genotype of rs217727 was associated with significantly decreased risk of breast cancer(P<0.05),and other genotypes of rs217727 had no correlation with the risk of breast cancer(P>0.05).TT genotype of rs2107425 was associated with significantly increased risk of breast cancer(P<0.05),and T allele had a significantly higher risk of breast cancer compared to C allele(P=0.002,OR=1.52,95%CI=1.17-1.98).TT genotype of rs2839698 had a significantly higher risk of breast cancer compared to CC genotype(P=0.03,OR=1.86,95%CI=1.06-3.25),and other genotypes of rs2839698 had no correlation with the risk of breast cancer(P>0.05).Further stratified analysis showed that CT+TT genotypes of rs217727 had a significantly lower risk of breast cancer among women who had the age of first birth more than 24years and the women in premenopausal(P=0.03,OR=0.49,95%CI=0.27-0.91;P=0.04,OR=0.52,95%CI=0.28-0.96,respectively).CT+TT genotype of rs2839698 had a significantly higher risk of breast cancer among women with no breastfeeding(P=0.03,OR=4.91,95%CI=1.17-20.67).No significant association between rs2107425 and age,reproductive factors and family history of breast cancer was observed in our study.Clinicopathologic analysis showed that CT genotype of rs217727 was significantly associated with ER positivity,and TT genotype of rs217727 was significantly associated with tumor size more than 5 cm(P=0.03,OR=2.22,95%CI=1.10-4.45;P=0.02,OR=2.45,95%=1.13-5.33,respectively).CT genotype of rs2839698 was significantly associated with ER positivity(P=0.02,OR=2.30,95%CI=1.16-4.57),TT/CT+TT genotypes of rs2839698 were significantly associated with tumor size more than 5 cm(P<0.05).However,no significant association between rs2107425/rs3741219 and clinicopathologic features of breast cancer were found(P>0.05).TT/CT+TT genotypes of rs2839698 were significantly associated with high level of H19 mRNA expression,and Western-Blot also showed a high level of Vimentin.Conclusion:The risk of breast cancer was significantly associated with genetic factors and reproductive factors.CT genotype of rs217727 was associated with significantly decreased risk of breast cancer,while TT genotype of rs2107425 and TT genotype of rs2839698 were associated with significantly increased risk of breast cancer.TT/CT+TT genotypes of rs2839698 were significantly associated with high level of H19 mRNA and Vimentin expression. |
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