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The Relationships Between GWAS-Identified SNPs For Colorectal Cancer And TNM Staging Of 316 Colorectal Cancer Cases

Posted on:2017-09-06Degree:MasterType:Thesis
Country:ChinaCandidate:J G ShiFull Text:PDF
GTID:2334330503990601Subject:Surgery
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Objective: To select the Single Nucleotide Polymorphisms(SNPs) identified by Genome-Wild Association Studies(GWAS) and associated with the risk of colorectal cancer(CRC). And then our focus was on analyzing the relationships between these SNPs and the TNM-staging of colorectal cancer, which might be a foundation to explore the potential molecular markers influencing the prognosis of CRC patients.Methods: Besides our previous researches, we circumspectly retrieved and read a large number of published GWAS in order to define the SNPs used in this research. All of the 316 participants were from hospitals in Wuhan and received the radical surgery of colorectal cancer between February, 2014 and December, 2015. We collected their peripheral blood samples and conducted the experiments of DNA extraction. And then we further genotyped these variants by the technology of Taq Man Genotyping Assay. Additionally, the clinical and pathological data were recorded systematically. We also compendiously followed up these participants for the disease-free survival. Statistical methods, such as 2c and test, unconditional logistic regression, were used for further analysis of the related data.Results: We included 19 SNPs and 316 cases with CRC in our study. 1. Analyses on general information: The average age of the 316 participants with CRC is 59.73±12.85 years old. Compared to the control group(T1+T2 or N0 or M1), there were no significant differences in the distribution of gender, age, smoking and drinking history for the case group(T3+T4 or N1+N2 or M1).2. The relationship between each locus and the T-staging of CRC: The genotypes of all the 19 loci were in accordance with the Hardy-Weinberg Equilibrium(HWE) rule for the control group(T1+T2). There were 4 variant loci(rs6687758, rs10505477, rs6983267 and rs7014346) found to be associated with the CRC's T-staging. Further stratified analyses showed that: in additive model, this correlation was still statistically significant(P < 0.05) for the four loci; in dominant model, only rs6687758 locus' SNP and in recessive model, rs10505477, rs6983267 and rs7014346 loci' s SNPs correlated significantly with the T-staging of CRC. 3. The relationship between each locus and the N-staging of CRC: For all the 19 loci, their genotypes also complied with the HWE rule. We found no variant locus that was significantly correlated with the CRC's T-staging(P > 0.050). In additive and dominant model, there was only one SNP showed correlation with the N-staging of CRC for each model. They were rs647161 and rs6687758, respectively. No significant locus was found in recessive model. 4. The relationship between each locus and the CRC's M-staging: Two variant loci(rs12603526 and rs2241714) didn't comply with the HWE rule and therefor were excluded in this analysis. Among the remaining 17 loci, all of them were not significantly associated with the M-staging of CRC. Further stratified analyses in all the three model mentioned above still showed no significant variant locus.Conclusions: For the 19 variant loci identified by GWAS, the SNP of rs6687758, rs10505477, rs6983267 and rs7014346 loci were correlated with the T-staging of CRC; rs647161 and rs6687758 loci's SNPs were associated with CRC's N-staging; We didn't find any locus that was correlated with the M-staging of CRC. Therefore, we should pay more attention to the relationships between the SNP of rs6687758, rs10505477, rs6983267, rs647161 and rs7014346 loci and the prognosis of CRC. Further researches would be needed for that.
Keywords/Search Tags:Colorectal Cancer, TNM-staging, GWAS, SNP, Case-control Study
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