The Association Between CTLA-4 Gene Polymorphism And The Risk Of Colorectal Cancer

Objective: This article intends to discuss the relationship between cytotoxic T lymphocyte-associated antigen 4 gene(CTLA-4) rs231775A/G and rs5742909C/T polymorphism and genetic susceptibility to the risk of Colorectal Cancer(CRC).Methods: Between February 2013 and February 2015 in the Fourth Affiliated Hospital of Hebei Medical University, 102 cases of colon cancer patients, 138 cases of rectal cancer patients and 147 healthy people were chosen to participate in the case-control study. We collected from the participants matching the conditions of the experiment, with their informed consent, venous blood of 5 ml, as well as their age, gender, smoking, drinking, family history and other information. The proteinase K digestion-saturated nacl salting out method was applied to extract the DNA in white blood cells, and polymerase chain reaction- ligase detection reaction(PCR-LDR) was used to detect CTLA-4 gene and analyze two SNP loci alleles and genotype of rs231775A/G and rs5742909C/T.SPSS Ver13.0 software kit(SPSS Company in New York, Chicago, Illionis, USA) was used for statistical analysis of the experimental result. T-test was conducted on age differences between rectal cancer group, colon cancer group and health control group; chi-square test was carried out on gender differences between the two groups and the distribution of allele frequency and genotype frequency distribution; Hardy-Weinberg equilibrium analysis was performed by comparing the observed and expected genotype; unconditional logistic regression method was applied to calculate the odds ratio(OR) of relative risk degree with 95% confidence interval(CI); and EH software and 2LD software were adopted to analyze the two SNPs of CTLA-4 gene, rs231775A/G and rs5742909C/T, with P<0.05 as the dividing line of a significant difference.Results:1 The genotype frequency distribution of rs231775A/G and rs5742909C/T met the Hardy-Weinberg equilibrium in the control group(P> 0.05).2 The analysis of correlation between CTLA-4 rs231775A/G polymorphism and the risk of CRCThe frequencies of alleles A and G on CTLA-4 rs231775 A/ G in the rectal cancer group were 10.9% and 89.1% respectively, while in colon cancer group they were 10.3% and 89.7%, and in control group 17.0% and 83.0%. There were statistical differences between the rectal cancer group and the control group, or between the colon cancer group and the control group(P was 0.035 in both cases). In the rectal cancer group, the frequencies of G/G and A/G were 83.6% and 16.4%, while they were 83.0% and 17.0% in colon group, and 71.8% and 28.2% in control group. There were statistical significant differences between the rectal cancer group and the control group or the colon cancer group and the control group(P were 0.019 and 0.044 respectively). Comparing with those with genotype AG, the people with genotype GG suffer a higher risk of colorectal cancer(OR = 1.966, 95% CI = 1.112-3.585, OR = 1.915, 95% CI = 1.012-3.621).3 The analysis of correlation between CTLA-4 rs5742909C/T polymorphism and the risk of CRC.The frequencies of the alleles C and T on CTLA-4 rs5742909C/T in the rectal cancer group were 79.7% and 20.3% respectively, while in colon cancer group they were 79.4% and 20.6%, and in control group 80.3% and 19.7%. There were no statistical difference between the rectal cancer group and the control group, or between the colon cancer group and the control group(P were 0.867 or 0.814 respectively). In the rectal cancer group, the frequencies of the genotypes CC and CT genotype were 63.0% and 37.0% respectively, while they were 67.0% and 33.0% in colon group, and 66.2% and 33.8% in control group. And there was no statistical difference between the rectal cancer group and the control group, or between the colon cancer group and the control group(P were 0.574 and 0.896 respectively). Therefore, no statistical difference existed to support the argument that Comparing with those with genotype CC, people with genotype CT have a higher risk of developing rectal cancer(OR=0.868, 95%CI=0.530-1.421); nor was there any statistical difference to support the argument that comparing with those with genotype CC, people with genotype CT shall suffer no higher risk of developing colon cancer(OR=1.037, 95% CI=0.600-1.794).4 EH software and 2LD software were adopted to analyze the two SNPs of CTLA-4 gene, rs231775A/G and rs5742909C/TIn colorectal cancer patients, there was linkage disequilibrium between rs231775A/G and rs5742909C/T(D’=0.809). The most frequent haplotype in control group was rs231775G-rs5742909C(63.2%), followed by rs231775A-rs5742909T(17.3%), rs231775A-rs5742909C(17.1%), and rs231775G-rs5742909T(2.5%); the haplotype rs231775G-rs5742909 T can reduce the incidence of colorectal cancer(OR=0.203, 95% CI=0.048-0.869); and the haplotypes rs231775G-rs5742909C(OR=0.976, 95% CI=0.723-1.319), rs231775A-rs5742909T(OR=1.192, 95% CI=0.818-1.737), rs231775A- rs5742909C(OR=0.991, 95% CI=0.674-1.458) have nothing to do with the risk.Conclusion:1 The gene polymorphism of CTLA-4 rs231775A/G may be associated with genetic susceptibility to colorectal cancer in the Hebei populations:Rs231775 allele G increased the risk of colorectal cancer;Comparing with AG genotype, the GG genotype increased the risk of colorectal cancer.2 The gene polymorphism of CTLA-4 rs5742909C/T was not associated with genetic susceptibility to colorectal cancer in the Hebei populations.3 There existed linkage disequilibrium between CTLA-4 rs231775A/G and rs5742909C/T. The haplotype rs231775G-rs5742909 T could reduce the incidence of colorectal cancer.