The Association Of Survivin Polymorphism With The Risk Of Colorectal Cancer

Objective: Survivin is an inhibitor of apoptosis protein,which locksapoptosis induced by a variety of triggers.Survivin plays an important role incell cycle regulation,and may be involved in the development and progressionof cancers.The expression of survivin is ubiquitous in fetal issues,but isnegligible in the majority of terminally differentiated adult tissues. Single-nucleotide polymorphisms(SNP) are inheritable mutation and had steadyorrelation with various diseases.Several polymorphisms in survivin promoterhave been dentified previously.These SNPs might be correlated with the riskof tumors.The study was designed to investigate the correlation of Survivinrs9904341C/G,rs8073069C/GSNPs with the risk of CRC. By this way, wehope to offer some evidences for the prevention and therapy of CRC atmelocularbiological level.Methods: This population-based case-control study included182CRCpatients and200healthy controls.The genomic DNA was extracted by usingproteinase K digestion followed by a salting out procedure.Genotypes of theSurvivin gene were analyzed by polymerase chain reaction-ligase detectionreaction (PCR-LDR) method.Statistical analysis was performed using SPSS11.5software package. Aprobability level of5%was considered significant for all statistical analyses.Hardy-Weinberg analysis was performed by comparing the observed andexpected genotype frequencies in study groups using Chi-square test.Univariate comparisons of allele and genotype distribution in cases andcontrols were performed by means of two-sided contingency tables usingChi-square test.The Survivin haplotype frequencies and linkage disequilibriumcoefficient were estimated by using EH linkage software and2LD software.The odds ratio (OR) and95%confidence interval (CI) were calculated using an unconditional logistic regression model.Results:1The genotype frequencies of Survivin rs9904341C/G and rs8073069C/Gin healthy controls did not significantly deviate from that expected for aHardy-Weinberg equilibrium (P＞0.05).2The frequencies of the Survivin rs9904341C/G C and G allele among CRCpatients and healthy controls were59.3%,40.7%和49.7%,50.3%,respectively;There was significant difference between the two groups (P=0.008,OR=1.474,95％CI=1.107~1.963).The distribution of the C/C,C/G and G/G genotypesbetween CRC patients (38.5%,41.8%and19.8%, respectively) and controls(26.5%,46.5%and27.0%,respectively) had significant difference (P=0.033).The frequencies of the C/C genotype of the Survivin rs9904341C/G weresignificantly higher in CRC patients (38.5%) than those in healthy controls(26.5%).Compared with the C/C genotype,the C/G and G/G genotypes couldsignificantly reduce the risk of developing CRC,the odds ratio were0.621(95％CI=0.389~0.992)and0.507(95％CI=0.292~0.882).When stratified forsmoking status, the C/G genotype significantly reduced the risk of developingCRC among smoking patients compared with the C/C genotype with the ORof0.310(95％CI=0.119~0.808)respectively.No significant difference in theG/G genotype and the risk of developing CRC among smoking patientscompared with the C/C genotype with the OR of0.334(95％CI=0.103~1.083)respectively.When stratified for drinking status,the C/G genotype significantlyreduced the risk of developing CRC among drinking patients compared withthe C/C genotype with the OR of0.261(95％CI=0.090~0.754)respectively.Nosignificant difference in the G/G genotype and the risk of developing CRCamong drinking patients compared with the C/C genotype with the OR of0.380(95％CI=0.103~1.407)respectively.No significant difference in genotypeand allele distributions was found between patients and control groups inSurvivin rs9904341C/G (P>0.05),when stratified for non-smoking andnon-drinking status.3The frequencies of the Survivin rs8073069C/G C and G allele among CRC patients and healthy controls were30.5%,69.5%and27.8%,72.3%respectively; No significant difference in the Survivin rs8073069C/G alleledistribution was shown between CRC patients and controls (P=0.404).Thedistribution of the C/C,C/G and G/G genotypes between CRC patients (11.0%,39.0%and50.0%, respectively) and controls(9.0%,37.5%and53.5%,respectively) also had no significant differrence(P>0.05).Compared with theC/C genotype,the C/G and G/G genotypes could not increase the risk ofdeveloping CRC,the odds ratio were0.850(95％CI=0.420~1.740) and0.770(95％CI=0.380~1.530.No significant difference in genotype and alleledistributions was found between patients and control groups in Survivinrs8073069C/G (P>0.05),when stratified for smoking and drinking status.4The combined effect of Survivin rs9904341C/G and rs8073069C/G SNPswas analyzed by EH and2LD software.The results showed that Survivinrs9904341C/G and rs8073069C/G polymorphisms were link disequilibrium(D'=0.628).The result showed that the rs9904341C-8073069G haplotype wasthe most common, which was49.8%.The rs9904341C-8073069C haplotypeincrease the risk of CRC.Compared with rs9904341C-8073069C haplotype,The rs9904341G-8073069C haplotype reduce the risk of CRC.Two otherhaplotypes would not change onset risk of CRC.Conclusions:1The Survivin rs9904341C/G SNP was associated with the risk ofdeveloping CRC.The C/C genotype significantly increased the risk ofCRC,The C/G and G/G genotypes could significantly reduce the risk ofdeveloping CRC.The subjects, particularly smokers or drinkers,carryingC/G and G/G genotypes could be associated with the reduced risk ofdeveloping CRC.2The Survivin rs8073069C/G SNP might not be associated with the risk ofCRC development.3The Survivin rs9904341C/G and rs8073069C/G SNP was imperfectly inlinkage disequilibrium.The rs9904341C-8073069C haplotype increase therisk of CRC. Compared with rs9904341C-8073069C haplotype.The rs9904341G-8073069C haplotype reduce the risk of CRC.Two otherhaplotypes distribution had no influence on the risk of CRC.