| Objective: Cysteine aspartic acid specific protease 3(Caspase3) belongs to the Caspase family and is a member of cell apoptosis gene. Originally it were found in caenorhabditis elegans genetics research development process as a cell apoptosis gene related to cell death. It were in common expression in human tumor tissues and normal tissues, and play a role in the development of cell such as proliferation, differentiation apoptosis. Through case- control study, this study discussed the relationship between polymorphisms of the two loci gene which is rs12108497 and rs4647693 on the Caspase3 and colorectal cancer(Colorectal Cancer, CRC).It could offer a new way for prevention and treatment of colorectal cancer.Methods: Through case-control study,this study selected 209 cases of rectal cancer patients,164 cases of colon cancer patients and 202 healthy people between Feb. 2014- Feb. 2016 in the fourth hospital of Hebei Medical University. Research objects in this experimental condition were collected venous blood of 5 ml on their own. gender, smoking, drinking, family history and other information were considered. This experiment adopts the proteinase K digestion- saturated sodium chloride salting out method to extract the DNA in white blood cells,The Polymerase Chain Reaction- ligase detection Reaction(Polymerase Chain Reaction- ligase detection Reaction, PCR- LDR) method was adopted to analyze Caspase3 gene and two SNP loci alleles and genotypes of rs4647693 A/G and rs12108497 C/T.Experiment data used SPSS Ver19.0 software package(SPSS Company in New York, Chicago, Illionis, USA) for statistical analysis. The differences of age in rectal cancer, colon cancer group and health control group were conducted by t-test. And gender differences between the two groups and the distribution of allele frequency and genotype frequency distribution used the chi-square test, respectively. Hardy-Weinberg equilibrium analysis was performed by comparing the observed and expected genotype. By unconditional logistic regression method to calculate represents the ratio of relative risk degree than(odds thewire, OR) and 95% confidence interval(the confidence interval, CI). Using EH software and 2 ld Caspase3 gene analysised the two SNPs of rs4647693A/G、rs12108497 C/T with P<0.05 as a significant difference in the standards.Results:1 In the selected control group, law of Hardy-Weinberg was used to analyzed the genotype distribution of sites rs12108497 C/T and rs4647693A/G(P > 0.05).2 Allele polymorphism analysis of rs12108497 C/T is related to colorectal cancer risk.Analyze the frequencies of C and T on Caspase3- rs12108497 C/T in each group. These in control group were 24.1% and 75.9%. Frequencies of Cases group including rectal cancer and colon cancer group were 33.8%, 66.2% and 33.2%,66.8% respectively. Contrast the control group and cases groups respectively, There were statistically significant differences between the rectal cancer group and the control group or the colon cancer group and the control group(P <0.05 and P <0.05, respectively). The genotype frequency of TT, CT, and CC in rectal cancer group and control group were 71.4%、19.1%、9.5% and 58.3%、26.8%、14.9%, There was statistical significance(P <0.05).The CT and CC increased the risk of colorectal cancer compared with TT,(OR = 1.672,95% CI = 1.010-2.630).While they were 59.3%、25.3% and 15.4% in colon group, There were statistically significant differences between the control group and the control group in CC genotype(P <0.05). Individuals who have genotype CC suffer more risk of colon cancer than that with genotype TT(OR=1.946,95%CI=1.016-3.729).3 Analyze the relation between Caspase3- rs4647693A/G polymorphism and CRC.The frequencies of A and G of Caspase3-rs4647693A/G in control group and the rectal cancer group were 11.3%、88.7% and 16.3%、83.7%. While they were 12.5% and 87.5% in colon cancer patients. There were statistically significant differences between the control group and the rectal cancer patients(P=0.040). But there were no statistically significant differences between colon cancer group and the control group(P=0.162). In the rectal cancer group, Frequencies of the GG and AG genotype were 77.4% and 22.6% in control group, while 64.5% and 36.5% in rectal cancer patients, and they were 69.8%、30.2% in colon group.There were statistically significant differences between the rectal cancer group and the control group(P=0.025).But not the colon cancer group and the control group(P=0.100). The AG genotype may increase the risk of rectal cancer but it had no correlation with colon cancer(OR=1.650,95%CI=1.062-2.564 and OR=1.484,95%CI=0.926-2.379).4 Analyze the relationship between rs12108497C/T and rs4647693A/G gene by software EH and 2LD in the matter of risks.There was linkage disequilibrium between Caspase3-rs12108497C/T and Caspase3-rs4647693A/G in rectal cancer patients and control group. The haplotype frequency of the rs12108497T-rs4647693 G was the hightest in the normal control group and in rectal cancer group(80.1% and 65.5%),followed by rs12108497T-rs4647693A(10.3% and 19.7%), rs12108497C-rs4647693G(6.6% and 11.2%), and rs12108497C-rs4647693A(3.0% and 3.6%). The incidence of colorectal cancer may be increased by the haplotypes of rs12108497T-rs4647693 A,rs12108497C-rs4647693 G,and rs12108497C-rs 4647693 A.The OR values and 95% CI of them were 1.343(1.109~3.449)、1.280(1.092~3.075) and 1.849(1.306~4.9144). There was no correlation between rs12108497T-rs4647693 G haplotype and the risk of colon cancer,because the OR values and 95% CI of rs12108497T-rs4647693 G haplotype was 0.753(0.416~1.882).There was linkage disequilibrium between Caspase3-rs12108497C/T and Caspase3-rs4647693A/G in colon cancer patients and control group. The haplotype of rs12108497T-rs4647693 G was the most frequent.The haplotype frequencies of the control group and rectal cancer patients were 74.9% and 60.2%,with other haplotype frequencies of rs12108497T-rs4647693A(15.6% and 24.4%), rs12108497C-rs4647693G(6.9% and 11.4%) and rs12108497Crs4647693A(2.6% and 4.0%). The combined analysis indicated that the haplotypes of rs12108497T-rs4647693 A, rs12108497C-rs4647693 G and 12108497C-rs4647693 A may increase the incidence of colorectal cancer. The OR values and 95% CI of them were 1.291(1.132~3.062), 1.152(1.051~2.754) and 1.832(1.386~4.816).The haplotype of rs12108497T-rs4647693 G had no correlation with the risk of colon cancer. Because the OR values and 95% CI of it were 0.832(0.323~1.214).Conclusion:1 The gene polymorphism of Caspase3 rs12108497C/T could be related to the risk of colorectal cancer in our country.The CC and CT genotypes increased the the risk of rectal cancer and the CC genotype increased the risk of rectal cancer.2 There may exsite a relationship between the gene polymorphism of Caspase3 rs4647693A/G and the risk of colorectal cancer. The AG genotype could increase the risk of rectal cancer.It could have no relation with colon cancer.3 It may have linkage disequilibrium between rs12108497C/T and rs4647693A/G in groups. |
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