IGFBP7Gene Polymorphisms Associated With Risk Of Colorectal Cancer

Objective: Insulin-like growth factor binding protein7(IGFBP7)belongs to the IGFBP family and is a member of insulin-like growth factoraxis. Originally it were cloned in the brain meningioma for its differentiallyexpressed. It were expressed in a variety of human normal tissues and tumortissues, and participated in the process of cell proliferation, growth, aging,apoptosis. We studied the relationship between polymorphisms of the two locigene which is rs11133472and rs1718848on the IGFBP7and colorectalcancer (Colorectal Cancer, CRC). This could provide theoretical basis forprevention and intervention in colorectal cancer.Methods: Between Feb.2012-Feb.2014in the fourth affiliated hospitalof Hebei Medical University,143cases of colorectal cancer patients,68casesof colon cancer patients and132healthy people were chosed in case-controlstudy. Objects matched the conditions of the experiment were collectedvenous blood of5ml voluntarily, and then were recorded age, gender,smoking, drinking, family history and other information. The proteinase Kdigestion-saturated nacl salting out method extracted the DNA in white bloodcells, and the Polymerase Chain Reaction-ligase detection Reaction(PCR-LDR) was used to detect IGFBP7gene and analyze two SNP loci allelesand genotype of rs11133472A/G and rs1718848A/G.Experiment data used SPSS Ver13.0software package (SPSS Companyin New York, Chicago, Illionis, USA) for statistical analysis. The differencesof age in rectal cancer, colon cancer group and health control group wereconducted by t-test. And gender differences between the two groups and thedistribution of allele frequency and genotype frequency distribution used thechi-square test, respectively. Hardy-Weinberg equilibrium analysis wasperformed by comparing the observed and expected genotype. By unconditional logistic regression method to calculate represents the ratio ofrelative risk degree than (odds thewire, OR) and95%confidence interval (theconfidence interval, CI). Using EH software and2ld IGFBP7gene analysisedthe two SNPs of rs1718848A rs11133472A/G/G with P<0.05as a significantdifference in the standards.Results:1Genotype distribution frequency of IGFBP7-rs11133472A/G andIGFBP7-rs17188484A/G obeyed the Hardy-Weinberg equilibrium in thecontrol group (P>0.05).2The analysis on polymorphism of IGFBP7-rs11133472A/G and pertinenceof CRCThe frequencies of alleles A and G on IGFBP7-rs11133472A/G in therectal cancer group were5.9%and94.1%respectively,while these in coloncancer group were6.6%and93.4%respectively. In control group these were2.3%and97.8%. There were statistically significant differences between therectal cancer group and the control group or the colon cancer group and thecontrol group (P was0.032and0.030, respectively). In the rectal cancer group,the frequencies of G/G and A/G were88.1%and11.9%, while they were86.8%and13.2%in colon group, and95.5%and4.5%in control group. Therewere statistically significant differences between the rectal cancer group andthe control group or the colon cancer group and the control group (P was0.028and0.027, respectively).The individual who has genotype A/G suffersmore risky of colorectal cancer than that who has the genotype G/G (OR=2.833,95%CI=1.082-7.421, OR=3.203,95%CI=1.090-9.417).3The analysis of correlation between IGFBP7-rs11133472A/G polymorphismand CRC.The frequencies of the alleles A and G on IGFBP7-rs17188484A/G inthe rectal cancer group were11.9%and88.1%, while in colon cancer groupthey were12.5%and87.5%. In control group they were6.4%and93.6%.There were statistically significant differences between the rectal cancer groupand the control group or the colon cancer group and the control group (P was 0.028or0.040respectively). In the rectal cancer group, frequency of thegenotypes G/G and A/G genotype were76.2%and23.8%, while75.0%and25.0%in colon group, and they were87.1%and12.9%in control group.Andthere were statistically significant differences between the rectal cancer groupand the control group or the colon cancer group and the control group (P was0.020and0.031, respectively). Compared with the genotype G/G,the genotypeA/G could significantly increase the risk of developing colon cancer(OR=2.110，95%CI=1.114-3.995；OR=2.255，95%CI=1.066-4.768).4The combined analysis on SNPs of rs11133472A/G and rs1718848A/G inIGFBP7gene was carried out by software EH and2LD.4.1In rectal cancer group and normal control group, there is strong chainimbalance between IGFBP7-rs1133472A/G and IGFBP7-rs1718848A/G. Andthe haplotype of rs11133472G-rs1718848G is the most common one.Thefrequencies of it in the normal control group and in rectal cancer group were84.8%and64.8%, followed by rs11133472G-1718848A (10.6%and20.3%),rs11133472A-rs1718848G (2.3%and9.8%), and rs11133472A-rs1718848A(2.3%and2.1%). The haplotypes of rs11133472G-1718848A, rs11133472A-1718848G and rs11133472A-1718848A could increases the risk of colorectalcancer.Their OR values and95%CI were1.365(1.109~3.449)、1.250(1.092~3.075) and1.946(1.306~4.914). The OR values and95%CI ofrs11133472G-1718848G haplotype was0.735(0.416~1.8820). This resultcould indicate that the haplotype of rs11133472G-1718848G may be nothingto do with the risk of colon cancer.4.2In colon cancer group and normal control group there is strong chainimbalance between IGFBP7-rs1133472A/G and IGFBP7-rs1718848A/G. Theresults showed that the highest frequency of haplotype was rs11133472G-rs1718848G.The frequencies of the haplotype one in the normal control groupand in rectal cancer group were75.0%and64.7%. In colon cancer group, thefrequencies of rs11133472G-1718848A, rs11133472A-rs1718848G andrs11133472A-1718848A were19.3%,3.8%and1.9%, while the frequenciesof these were22.1%,10.3%and2.9%. The results showed that the three haplotypes of rs11133472G-1718848A, rs11133472A-rs1718848G andrs11133472A-1718848A could increases the risk of colorectal cancer. TheirOR values and95%CI were1.365(1.109~3.449),1.250(1.092~3.075) and1.946(1.306~4.914). The OR values and95%CI of haplotype ofrs11133472G-1718848G were0.735(0.416~1.8820). Due to the smallsample size of rs11133472G-1718848G haplotype may be nothing to do withthe risk of colon cancer.Conclusion:1IGFBP7rs11133472AG,rs1718848AG genes increased the risk ofcolorectal cancer. Rs11133472GG and rs17188484GG genotype may havenothing to do with the risk of colorectal cancer.2There exsited a linkage disequilibrium between SNPs of rs11133472and SNPs of rs1718848.The risk of colorectal cancer may increase whenrs11133472and rs1718848have any mutation genotype.