The Association Between SNP In Cancer-related Genes 3’UTR Of Luzhou Population And Susceptibility To Colorectal Cancer

Background: Colorectal cancer(CRC) is the third most common type of cancer. in China, cancer is the first leading cause of major disease-related mortality, and colorectal cancer ranks fifth of the most harmful cancer. because of the stealthiness of the tumor, it is generally middle and advanced stage when we diagnosis it, it have irreversible effects on survival and quality of life of patients. Therefore, the researches of pathogenesis of colorectal cancer, to find the molecular markers of their early diagnosis, prevention and prognostic are particularly important.Colorectal cancer is a complex multifactorial diseases, involving multigene. Single nucleotide polymorphisms(SNP) is widely distributed in the human genome, its minor allele frequency(MAF)>0.1, which can better reflect the individual individual differences in genetic background. In recent years, the development of biological information technology and the success of the human genome project provide a large number of SNPs genetic information and the techniques achieve fast, technical means of automation and large-scale testing of SNPs, so that SNPs have broad application prospects in prognosis of tumors. Currently, it has been found more than 10 million SNPs in the human genome, a considerable part of polymorphic loci located in 3’untranslated region(3’UTR). Recent studies have confirmed that these SNPs which located in the 3’UTR may affect m RNA stability by influencing the micro RNA(mi RNA) and other binding protein combine to m RNA and changing conformation of m RNA, thus they can take part in post-transcriptional regulation of target genes.The purpose of this study is to investigate SNPs located in the 3’UTR of colorectal cancer-related genes, analyze the correlation with clinicopathological features of colorectal cancer, to offer practical reliable theory for colorectal cancer prevention, early detection, early diagnosis, provide a theoretical basis for the molecular mechanism and regulation of gene expression in colorectal cancer progressing.Materials and Methods: In this "case-control" study,(1) the 371 colorectal cancer cases are Han population of Luzhou which confirmed by pathological diagnosis, and we collect personal information of them, including name, gender, age, smoking status, alcohol consumption and family history; history of surgery; pathological data. At the same time,we determine 246 cases of healthy subjects as controls whose gender and age matched the case;(2) we use public database, including the national institute of environmental health sciences(NIEHS), the US national center for biotechnology information(NCBI) and the international SNPs in public databases resource platform website hap map project(Hapmap) to achieve the preliminary screening of bioinformatic and the function prediction of single nucleotide polymorphisms located in 3’UTR of colorectal cancer-related genes APC, KRAS, VEGF, TGFBR1;(3) using i MLDR to test SNPs genotyped of 637 DNA samples;(4) investigating the correlation between candidate SNPs and risk of colorectal cancer, pathological parameters(tumor location, size, gross type, histological type, depth of invasion, differentiation, TNM stage) by the chi-square test and t test; using goodness-of-fit chi-square test to analyze whether the genotype frequencies distribution of cases and controls were in line with H-W equilibrium; analysising linkage disequilibrium and haplotype distribution of candidate SNPs by haploview 4.0 software and SHEsis-online.Results:(1) epidemiological data: age, gender distribution, smoking and alcohol consumption was no significant difference between colorectal cancer group and the healthy control group(p>0.05).(2) All SNPs were in Hardy-Weinberg equilibrium(p>0.05).(3) The difference of allele(rs334348、rs334349 、 rs3025039 、 rs3025040 and rs1804197) frequency distribution between colorectal cancer patients and healthy control group was statistically significant(p<0.05).(4) The analysis of SNPs genotype polymorphism: rs3025040 CC / CT + TT genotype OR = 0.696(0.489 ~ 0.992), rs1804197 CC / AA + AC genotype OR = 1.584(1.130 ~ 2.220).(5) The study did not find a susceptibility haplotype of colorectal cancer in candidate genes.Conclusions:(1) the rs1137188 and rs9266 in KRAS, rs334348 and rs334349 in TGFBR1, rs3025039 and rs3025040 in VEGF have entirely linkage disequilibrium.(2) The rs334348, rs334349 located in TGFBR1 3’UTR are associated with susceptibility of colorectal cancer. The individuals who carry A allele of rs334348 and G allele of rs334349 had a high risk of colorectal cancer.(3) The rs3025039, rs3025040 located in VEGF 3’UTR were associated with susceptibility of colorectal cancer, the individuals who carry T allele had a high risk of colorectal cancer. Compare to CC, TT+CT genotype increased the risk of colorectal cancer(4) VEGF gene 3’UTR polymorphisms rs10434, rs3025053 were not associated with susceptibility of colorectal cancer.(5) There was no correlation between APC 3’UTR polymorphism rs41116 and the susceptibility of colorectal cancer. The APC 3’UTR polymorphism rs1804197 was associated with susceptibility of colorectal cancer, the C allele and CC genotype increased the risk of colorectal cancer.(6) KRAS gene 3’UTR polymorphisms rs1137188, rs9266 were not associated with susceptibility of colorectal cancer.