Identification Of Novel Variants And Association Investigation Of The SNPs With Clinical Pathology Of Metadherin In Voarian Cancer

Objective:The aim of this study was to identify novel variants of metadherin(MTDH) and investigate the association of the SNPs in MTDH with clinical pathology and susceptibility of ovarian cancer.Methods:Genomic DNA extracted from blood samples of 52 patients operated on between 2008 and 2009 at Qilu Hospital of Shandong University for treatment of ovarian cancer, and 100 health persons located at same region as control group. Amplified by polymerase chain reaction(PCR) and sequenced to find novel variants. Analysis sequence data with Meglign7.0 and Chromas2.33 and statistic analysis with SPSS 13.0. All p value were exacter two-side and p value of<0.05 were considered statistically significant.Result:There were no significant clinical different in age and menstrual history for the 2 group. Variants were detected in 12 ovarian cancer cases and 13 controls. Among all the variants detected,5 novel variants were diccovered. All of the known and novel variants were re-sequenced and tested by public statistical web-tool,OEGE on the Hardy-Weinberg model with a p value>0.5. All the novel variants (—405C>T,1G>A,2678G>T,3467C>T,3503A>T, named ns1-5 in turn)appeared to gather at both ends of MTDH gene and low frequency. Among all the rest variants detected,3SNPs(rs2438211,rs244912,rs1311) located at 3'UTR of exon12 were found with complete linkage in both groups. Between the ovarian cancer group and control group, there was no significant difference in the distribution of genotypes and the frequencies of the two alleles at all SNPs(P>0.05), and no significant linkage was found between the variants with susceptibility of ovarian cancer. But significant difference was found between ovarian cancer of early stage and late stage in the frequencies distribution in SNPs(1681G>A,2928C>T, 3088A>G,3540T>C)of MTDH(P<0.05).Conclusion:5 novel variants were diccovered in MTDH. The variants associated with susceptibility of ovarian cancer were not identified, but the frequencies of the two alleles at 4 knowed variants of MTDH were associated with the grade of ovarian cancer.