The Association Between CD28 Gene Polymorphism And The Risk Of Colorectal Cancer

Objective: This article intends to discuss the relationship between CD28 rs3116496C/T and rs3181098A/G 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 the Cleaved Amplification Polymorphism Sequence-Tagged Sites(CAPs or PCR-RFLP) was used to detect CD28 gene and analyze two SNP loci alleles and genotype of rs3116496C/T and rs3181098A/G.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 CD28 gene, rs3116496C/T and rs3181098A/G, with P<0.05 as the dividing line of a significant difference.Results:1 The genotype frequency distribution of rs3116496C/T and rs3181098A/G met the Hardy-Weinberg equilibrium in the control group(P> 0.05).2 The analysis of correlation between CD28 rs3116496C/T polymorphism and risk of CRCThe frequencies of alleles C and T on CD28 rs3116496C/T in the rectal cancer group were 11.6% and 88.4% respectively, while in colon cancer group were 10.8% and 89.2% respectively. In control group these were 6.1% and 93.9%. There were statistically differences between the rectal cancer group and the control group or between the colon cancer group and the control group(P was 0.021 and 0.049 respectively). In the rectal cancer group, the frequencies of TT and CT were 78.1 and 21.9%, while they were 82% and 18.0% in colon group, and 87.8 and 12.2% in control group. There were statistically significant differences between the rectal cancer group and the control group(P was 0.03). But There were no statistically differences between the colone cancer group and the control group(P was 0.208). The individual who has genotype CT suffers more risky of rectal cancer than that who has the genotype TT(OR=2.009,95%CI=1.062-3.803).3 The analysis of correlation between CD28 rs3181098A/G polymorphism and risk of CRC.The frequencies of the alleles G and A on CD28 rs3181098A/G in the rectal cancer group were 78.6% and 21.4%, while in colon cancer group they were 76.5% and 23.5%. In control group they were 75.9% and 24.1%. There were no statistical difference between the rectal cancer group and the control group or the colon cancer group and the control group(P was 0.430 or 0.873 respectively). In the rectal cancer group, frequency of the genotypes GG and AG genotype were 64.4% and 35.6%, while 62.5% and 37.5% in colon group, and they were 62.8% and 37.2% in control group. And there were no statistical difference between the rectal cancer group and the control group or the colon cancer group and the control group(P was 0.783 and 0.966 respectively). Compared with the genotype GG, the genotype AG did not increase the risk and no statistical difference of developing colonrectal cancer(OR=0.932,95%CI=0.567-1.533;OR=1.012,95%CI=0.590-1.735).4 EH software and 2LD software were adopted to analyze the two SNPs of CD28 gene, rs3116496 C/T and rs3181098 A/G.In colorectal cancer patients, there was linkage disequilibrium between rs3116496 C/T and rs3181098 A/G(D’=0.994). The most frequent haplotype in control growp was rs3116496T-rs3181098G(69.7%); And followed were: rs3116496T-rs3181098A( 24.1%), rs3116496C-rs3181098G( 6.1%), rs3116496C-rs3181098A(0%). The haplotype of rs3116496C-rs3181098 A and rs3116496C-rs3181098 G could increase the incidence of colorectal cancer(OR=86.208, 95%CI=4.834-1537.469;OR=1.806, 95%CI=1.032-3.159); The haplotype of rs3116496T-rs3181098A(OR=0.864, 95%CI=0.612-1.219)and rs3116496T-rs3181098G( OR=0.889, 95 % CI=0.649-1.216) were unrelated to the diseases.Conclusion:1 The gene polymorphism of CD28 rs3116496 C/T may be associated with genetic susceptibility to colorectal cancer in the Hebei populations: rs3116496 allel C increased the risk of colorectal cancer; compared with TT genotype, the CT genotype increased the risk of rectal cancer.2 The gene polymorphism of CD28 rs3181098A/G was not associated with genetic susceptibility to colorectal cancer in the Hebei populations.3 There exsited linkage disequilibrium between CD28 rs3116496 C/T and rs3181098A/G. The haplotype of rs3116496C-rs3181098 G could increase the incidence of colorectal cancer.