TLR4Gene Polymorphisms Associated With Risk Of Colorectal Cancer

Objective: Toll-like receptors is a transmembrane receptor signaltransmission discovered recently as an important pattern recognition receptors(PRRs)，which plays an important role in various diseases.Polymorphismsaffect the body’s disease susceptibility.TLR4are closely linked with a varietyof diseases as a transmembrane receptor.We try to discuss the relevance of thesingle nucleotide polymorphism (SNP) of TLR4gene rs1927914andrs10759932two sites and colorectal cancer (CRC) correlation risk through thecase-control study, providing a favorable molecular basis for the diagnosis andtreatment of 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 choosed in case-controlstudy. Objects meet the conditions for the experiment collected venous bloodof5ml, and record the age, gender, smoking, drinking, family history andother information. The proteinase K digestion-saturated nacl salting outmethod to extract the the DNA in white blood cells, the Polymerase ChainReaction-ligase detection Reaction (PCR-LDR) was used to detect TLR4gene and rs1927914C/T rs10759932C/T two SNP loci alleles and genotype.Experiment data using SPSS Ver13.0software package (SPSS Company inNew York, Chicago, Illionis, USA) for statistical analysis. Age difference inrectal cancer, colon cancer group and health control group were conducted byt-test; And gender differences between the two groups and the distribution ofallele frequency and genotype frequency distribution using the chi-square test,respectively. Hardy-Weinberg equilibrium analysis was performed bycomparing the observed and expected genotype. By unconditional logisticregression method to calculate represents the ratio of relative risk degree than (odds thewire, OR) and95%confidence interval (the confidence interval, CI).TLR4gene in EH software and2ld-2026C/T rs1927914and rs10759932C/Gtwo SNPs with combined analysis, P <0.05as there are significant differenceof the standard.Results:1The distribution of the genotype frequencies of-2026rs1927914C/Tand-1607rs10759932C/T two loci were consistent with Hardy-Weinbergequilibrium (P>0.05).2TLR4gene rs1927914T/C polymorphism and colorectal cancer riskcorrelation analysisThe frequency of rs1927914C/T TLR4gene loci C and T in the coloncancer group was47.1%and52.9%,38.8%and61.2%in rectal cancer groupand41.3%and58.7%in control group, Compared in two groups, There werenot statistically significant difference in colorectal cancer and the controlgroup(P value was0.270and0.554), In the colon cancer group, C/C,C/T andC/T genotype frequency were20.6%,52.9%and26.5%, while17.4%,47.7%and10.8%in normal control group, no significant difference (P=0.479and0.626), compared with wild-T/T genotype,C/C genotype and C/T genotypecarriers have no correlation with the incidence of colon and rectal cancer(OR=1.342，95%CI=0.649-2.776；OR=0.957，95%CI=0.568-1.613).3Rs10759932C TLR4gene C/T polymorphism and colorectal cancerrisk correlation analysisThe frequency of TLR4gene rs10759932C/T locus allele C and T was30.8%and69.2%in colon cancer group,35.3%and65.7%in rectal cancergroup, in the normal control group were29.5%and70.5%, show that incontrast to colorectal cancer and in the control group, the difference wasstatistically no significant (P=0.474and P=0.238). In colon cancer,thefrequencies of C/C,C/T and T/T three kinds of genotype were7.4%,55.9%and36.8%, in rectal cancer were12.6%,36.4%and51%, while in the controlgroup were17.4%,25.3%and59.1%, show that in contrast to colon cancer andin the control group, the difference was statistically significant (P =0.001);rectal cancer group and control group for comparison, the differenceswere not statistically significant (P=0.059),Compared with wild T/Tgenotype,C/T genotype may reduce the risk of CRC （OR=0.261，95%CI=0.136-0.503；OR=0.558，95%CI=0.323-0.965），C/C genotype was notsignificant (OR=1.474，95%CI=0.507-4.285；OR=1.196，95%CI=0.597-2.395)4Combined analysis of TLR4colon cancer group and the control group ofgenes rs1927914C/T and rs10759932C/T two SNPs locus by EH software and2LD software. Display (Table7) unbalanced phenomenon linked TLR4geners1927914C/T and rs10759932C/T two loci (D’=0.994). Haplotype,rs1927914T-rs10759932Chaplotype(OR=0.846,95%CI=0.506~0.914), showedthat the genotype and colorectal cancer risk associated with. The otherhaplotypes of OR and95%CI were0.406(95%CI=0.009~18.820),0.716(95%CI=0.209~2.449), showed that the haplotypes may have nothing to dowith the risk of colorectal cancer.The combined analysis of TLR4gene in colorectal cancer group and thecontrol group rs1927914C/T and rs10759932C/T two loci SNPs, display(Table8) unbalanced phenomenon linked TLR4gene rs1927914C/T andrs10759932C/T two loci (D’=0.993). Four kind of monomers OR and95%CIwere0.598(95%CI=0.653~1.605),1.331(95%CI=0.519~3.413),1.024(95%CI=0.653~1.605),0.913(95%CI=0.579~1.439), showed that the fourhaplotypes may not be associated with the risk of colorectal cancer.Conclusion:1TLR4gene C-2026T(rs1927914) SNP may be not correlate to theincidence of CRC.2TLR4gene-1607(rs10759932) may be correlate to the incidence ofcolon cancer. Carrying the C/T genotype may reduce the risk of colon cancer.3TLR4gene rs1927914and rs10759932exsit a linkage disequilibriumbetween SNPs loci (D=0.994). Rs1927914T-rs10759932C haplotype canreduce colon cancer risk, the other haplotypes may not be associated with therisk of colon cancer. Analysing two sites of SNPs of TLR4geners1927914C/T and rs10759932C/T in rectal cancer group and the control group of (D’=0.993), the four kinds of haplotypes may not be associated withthe risk of colorectal cancer.The combined analysis of TLR4gene in colorectal cancer group and thecontrol group rs1927914C/T and rs10759932C/T two loci SNPs, display(Table8) unbalanced phenomenon linked TLR4gene rs1927914C/T andrs10759932C/T two loci (D’=0.993). Four kind of monomers OR and95%CIwere0.598(95%CI=0.653~1.605),1.331(95%CI=0.519~3.413),1.024(95%CI=0.653~1.605),0.913(95%CI=0.579~1.439), showed that the fourhaplotypes may not associated with the risk of colorectal cancer.