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[Abstract]:Background and objective colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system. According to the International Center for Cancer Research, there are 136 new cases of colorectal cancer in the world in 2012, and 69 cases of colorectal cancer deaths. In recent decades, the incidence of colorectal cancer has changed greatly in the world, and China is still a low-developing country of colorectal cancer in the last century. However, with the development of economic and social development and the transformation of the lifestyle, the incidence of colorectal cancer has increased significantly. It has become a major public health problem which is a serious threat to the health and the quality of life of our residents. The development of colorectal cancer is a multi-stage and multi-step process of environmental factors and genetic factors. The genetic variation of the genome can influence the function of the gene by changing the structure of the gene so as to exert different effects under the influence of the environmental factors, leading to the change of the susceptibility of the individual colorectal cancer. Long-chain non-coding RNA (lncRNA) is a class of RNA molecules that do not encode or rarely encode proteins between 200nt and 100kb. in view of the conservative secondary structure, the shear form, the subcellular localization, and the important biological functions of the expression level of the regulatory protein coding gene at various levels and in the development of tumor cell proliferation, apoptosis, migration and the like, Some of the sites of the ncRNA genetic polymorphism may be associated with the development of colorectal cancer and may be used as a biomarker for the assessment of genetic susceptibility to colorectal cancer. Materials and Methods The latest bioinformatics methods were used in this study to study the distribution characteristics of the genomic lncRNA genetic polymorphism sites and to design a two-stage case-control study based on the natural population in Jiashan County, Zhejiang Province. To analyze the association between the genetic polymorphism of lncRNA and the incidence of colorectal cancer. The inclusion of case-control was divided into two phases: a total of 320 cases and 319 cases were included in one stage, and 501 cases and 538 cases of colorectal cancer were included in two stages. The method of site-to-house survey was used to obtain the relevant information of the study object through face-to-face interview, and the database was established. At the same time, 5 ml of peripheral venous blood was collected, the genomic DNA was extracted, and the screened 102 ncRNA genetic polymorphism sites were detected by MassARRAY based on the Sequenom platform. The statistical software of S9.2, Stata 11.2 and R.13. 0 was used in the statistical analysis of this study. Results The results of the two-stage combined case-control study in this study included 821 cases of the case group and 857 in the control group. There was a statistically significant difference in the distribution of marital status, family tumor history and tea-drinking conditions in the case group and control group, and there was no statistically significant difference in sex, age, BMI, occupation, education level, smoking, and alcohol consumption. Using the latest human lncRNA database and the relevant information of the ncRNA expression profile database obtained from the previous research base of the research group, the information-complete genomic lncRNA SNPs database and the potential related lncRNA SNPs database of colorectal cancer were established. The results of the detection and classification of the screened genetic polymorphism sites are as follows: the distribution of the different genotypes of the polymorphic sites of the RP11-650L12. 2 rs149941240 is positively related to the risk of the rectal cancer, and the risk of colorectal cancer in the rs149941240 TTCC/ DEL-type carrier is increased by 47.1% compared with the TTCC/ TTC gene carrier, The risk of colorectal cancer in the TMCC/ DEL genotype and the DEL/ DEL genotype carriers increased by 40.6%. The distribution of the different genotypes of the polymorphic sites of the RP11-392P7.6 rs10845671 was positively correlated with the risk of the rectal cancer, and compared with the CC gene carrier, RP5-884M6. 1rs60226884 and rs10250402 polymorphism loci have a positive correlation with the risk of rectal cancer. Compared with the T/ T gene carrier, the risk of colorectal cancer in the rs60226884 T/ DEL-type carrier is 32.8%, compared with that of the GG gene carrier, The risk of colorectal cancer in rs10250402GT genotype was 34.3%. In addition, the distribution of P11-3N2. 1rs13230517 polymorphic site was negatively correlated with the risk of rectal cancer. Compared with the GG gene, the risk of colorectal cancer in the rs 13230517GA-type carrier decreased by 26. 1%. It was found that there was an interaction between the polymorphism of lncRNA gene and the above-mentioned lifestyle characteristics after the stratified analysis according to the characteristics of the living methods such as smoking, drinking and drinking tea. Conclusion The association between the genetic polymorphism of lncRNA and the susceptibility to colorectal cancer is analyzed in this study. The main findings are as follows: (1) There are 1173 SNP sites in the total of 11780 lncRNA in the genomic lncRNA SNPs database, and 65805 SNPs in the potential related lncRNA SNPs database of colorectal cancer have 1065 ncRNA. (2) The distribution of different genotypes of lncRNA RP11-650L12. 2rsl49941240, RP11-392P7. 6rs10845671, RP '5-884M6. 1rs60226884, rs 10250402 may increase the risk of colorectal cancer; the distribution of different genotypes of the genetic polymorphism sites of RP11-3N3.1 rs13230517 will reduce the risk of colorectal cancer. (3) There is a complex interaction between the distribution of the different genotypes of lncRNAMAGE2-AS3 rs6949538 and the conditions of smoking and tea drinking. These evidence suggests that lncRNA may be involved in the occurrence of colorectal cancer and its genetic polymorphism has potential as a molecular marker for colorectal cancer susceptibility. These findings remain to be further validated based on large sample prospective cohort studies and functional studies of the natural population.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.34

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