| Colorectal cancer is a common cause of cancer death in China. Many genes have been reported to be closely related with the carcinogenesis of colon and rectum. But evidence is accumulating to suggest that interactions between neoplastic cells and the surrounding microenvironment are crucial to each step of tumorigenesis. One of the proteins that play an essential role in the dynamics of maintaining the cellular microenvironment is the MMPs family. MMPs constitute a family of >26 proteolytic enzymes that are capable of selectively degrading a wide spectrum of both extracellular matrix and nonmatrix proteins. It is generally believed that the MMPs, via breakdown of the physical barrier, play a pivotal role in tumor invasion and metastasis. However, recent work has also suggested that, in addition to the historically considered features of promoting invasion and metastasis, MMPs also play an important role in several steps of cancer development. There are several routes whereby they can alter the cellular microenvironment and consequently affect the process of neoplastic transformation and tumor development.SNPs is single-base variation in DNA that occurs about once in every 1000 bases and the frequency of variation is more than 1%. SNPs can serve as genetic markers for identifying disease genes by linkage studies in families, association analysis ofpatients and controls. SNPs also have potential as direct functional polymorphic variants involved in common and genetically complex human disease and pharmagenetic traits.Recently, polymorphisms in the promoters of MMPs genes have been found. Some polymorphisms seem to influence expression levels and be associated with the development and/or progression of carcinomas of the ovary, endometrium, lung and stomach. However, there are no reports of the association between these polymorphisms and the development and progression of colorectal cancer in a Chinese population.DHPLC is recently developed cost-effective, rapid, sensitive and high-throughput technique for detection of mutations. In order to set up a method based on DHPLC for SNPs genotyping, we screened SNPs in the CDX2 promoter and coding regions. CDX2 is a member of the caudal-related homeobox gene family and it is specifically expressed in the intestine. Several studies suggest CDX2 has a potencial of tumor suppressor function. A cohort of 126 unrelated colorectal cancer cases were accrued from the affiliated hospital, Zhejiang University College of Medicine from January 2000 to September 2003. The tumor tissues and the histologically normal tissues in the distant margin to the tumor were collected at the time of surgery from patients who were undergoing resection of colorectal tumors. Healthy controls were recruited from routine check-up people who had no cancer history or family cancer predispositions. Controls were frequency-matched to the cases on sex and age (+ 5 years). Genomic DNA was prepared by digestion with proteinase K and phenol-chloroform extraction from surgically resected normal tissues in the distant margin to the tumor and the peripheral blood of the controls. PCR-based DHPLC and sequencing were used to determine the genotyping. Expectation maximization algorithm was used for haplotype frequencies analysis and pairwise linkagedisequilibrium test. Heterozygosity and polymorphism information content of simple site and multi-sites were also calculated. Chi-square test was used to test differences in the genotype distribution between the patients and the controls. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated as the estimate of the relative risk. Relations between the genotype and clinicopathological characteristics of colorectal cancer patients were calculated by Fisher's exact test. Inthis study, three SNPs : G48041C, T53685C, G53759T are identified in the CDX2promoter and coding regions, agreed with Hardy-Weinberg equilibrium. There is strong LD among these SNPs and site T53685C and G53759T are in complete LD. Genotype frequencies, allele frequencies and haplotype frequencies...
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