The Association Of The Snps In MiRNA-146A And MiRNA-122with Hereditary Predisposition And The Earlier Recurrence After Resection For Hepatocellular Carcinoma

The part IThe association of single nucleotide polymorphism in miRNA-122and in miRNA-146a with hereditary predisposition to HCCResearch backgroundThe miRNAs are the kind of short sequences of RNA. From a biological efficiency to judge, miRNAs regulation is more advanced and efficient. The studys have found that it actively participated in the biological behavior of tumors. But for those miRNAs related to global liver cancer research, their expression spectrum are not yet to be clear, the results of study don’t support each other.SNPS (single nucleotide polymorphism SNP) is a sequence polymorphism, caused by a single nucleotide mutation in sequence of chromosome genome. In general, the SNP is refers to the single nucleotide mutation of which the rate is more than1%, the mutation just is a site base changes. It is not only the genetic markers, but also may regulate the expression of genes that cause individual different reactions to physiological and pathological factors, which affect susceptibility to certain diseases. A SNP has different effects on different areas of the human race. Few experts abroad in recent years carry out the reach about HCC (hepatocellular carcinoma) susceptibility with SNPs in some miRNAs. Compared to HCC in China and abroad, considering the existing different region and more the hepatitis B virus infection backgroud in china HCC paitents, screening for liver cancer related literature,8miRNAs were selected for study. These miRNAs have been including in new study of HCC,or have been found with higher contact to association with HCC.This study try to find some SNPs in miRNAs which may realated to heredity predisposion to HCCMethodsThrough genebank,8miRNAs which were designed to two-directions primer were case-control reached in173cases surgical specimens of paraffin of hepatocellular carcinoma and41cases surgical specimens of paraffin of benign liver diseases,by extracting DNA; amplification by the PCR;analysis their sequence; looking for the SNP location of PCR products.A logistic regression model was constructed to evaluate outcome of experiment.Results1, In our designed sequence, miR-122SNPS location was found only one, which is located in the102base and in downstream of miR-122genomic code. The other eight sites were not found.In hsa-mir-122SNP location (rsl7669). C/C genotype, T/T genotype, and T/C genotype frequency distribution were:4%(7/173),63.6%(110/173) and32.4%(56/173), respectively. Compared to T/T genotype, hsa-mir-122SNPS location (rs17669) C/C genotype decreased significantly risk of HCC,and was protective factor for HCC (OR=0.213,95%CI:0.0627.390). 2, miR-146a SNP sites located in miR-146a gene encoding area, other nine SNP sites in gene bank were not found. Hsa-mir-146a SNP location (rs2910164) C/C genotype, G/G genotype and G/C genotype frequency distribution were respectively:35.3%(61/173),15.0%(26/173) and49.7%(56/173).Compred to G/G genotype in hsa-mir-146a SNP location (rs2910164),C/C genotype and C/G genotype were a risk factor for HCC (OR=3.086,95%CI:1.2897.390).3, In our designed sequence length,no SNP location were found in the rest4micrornas DNA sequence(miRNA-21、miRNA-183、miRNA-200c、 miRNA-375).Except for miR205and miR-210, which were not amplify succesfuly by PCR.Conclusion1, As for Jiangxi hans with infection of hepatitis B virus, SNP location (rs17669) and SNP Iocation(rs2910164) may be associated with hereditary predisposition to HCC.2, In designed sequence length, no SNP locations were found in the miRNA-21*. miRNA-183、miRNA-200c、miRNA-375; miRNA-210and miRNA-205did not amplified successfully by PCR. Part ⅡThe association of single nucleotide polymorphisms in miRNA-122and miRNA-146a with early postoperative recurrence of hepatocellular carcinomaResearch background Hepatocellular carcinoma (HCC)5years postoperative recurrence rate as high as40%-60%, which reveal poor curative effect, especially for the recent recurrence patients. With the progress of the genomics, it is possible that at the gene level find new risk factors which are effective and perfect supplement for clinical factors. Therefore, it is important to look for genetic indicators related early postoperative recurrence, which help doctors select the appropriate surgical cases. Therefore, the relationship with the more early recurrenc and the early recurrence of Postoperation in HCC patients and the SNP in miRNA should be reserched. At present, there is no syudy about SNP of miRNA associated with the prognosis of HCC surgery. Genetic susceptibility to HCC related gene polymorphism of change, make some individuals at the molecular level of congenital HCC, we hypothesized that:the two SNPs mentioned in the first part of the study, might influence the expression of related genes in some way; So, we further discussed the relationship between HCCsusceptibility2SNP located in the miRNA-122and the miRNA-146-a gene sequences, and recent recurrence and early postoperative recurrence of HCC.MethodsRecurrence in6months was defined as the more early recurrence, early recurrence was defined in2years. Case-control study of the above two different genotyping of miRNAs, multi-factor COX regression analysis of recent and early postoperative recurrence related factors, analyze the recurrence relations with different genotypes.ResultsRecurrence in6months was38.7%(67/173); Recurrence in12months was53.1%(92/173); Recurrence in24months was57.2%(99/173).By the cumulative recurrence analysis,the24months was peak of recurrence ofPostoperation,72%recurrence cases were in6months; The rs2910164C/G genotype was a risk factor for recurrence of liver cancer in the more early time and early time(OR=9.040,95%CI:2.393-34.155; OR=4.165,95%CI:1.898-9.141)..the The rs17669has nothing to do with the postoperative recurrenceConclusionThe rs2910164C/G genotype may associated with recent recurrence of HCC. The rs17669did not associated with recent recurrence of HCC.