Study Of Correlation Between SNPs In TLR9 Gene Promoter Region And Occurrence And Development Of Cervical Cancer

Objective:To evaluate the association of single nucleotide polymorphisms (SNPs) (rs352139 C>T、rs352140 C>T and rs5743836 A>G) in the promoter region of TLR9 gene with the occurrence and development of cervical cancer.Method:Under the principle of informed consent, 253 patients with cervical cancer, 92 patients with precancerous lesion and 330 health individuals were recruited in this study, and the SNPs were genotyped by TaqMan Assay. Additionally, the haplotypes were constructed and the association of the haplotypes with the occurrence and development of cervical cancer was analyzed.Results:1 .The allelic and genotypic frequency of these three SNPs showed no significant difference between cancer, CIN and control groups (P>0.05).2.There was a strong linkage disequilibrium between rs352139(C>T) and rs5743836(A>G) ,and rs352140 (C>T) and rs5743836(A>G) in the cancer group and control group according to the linkage disequilibrium analysis, D’>0.8.3. The frequencies of haplotypes constructed by rs352139 (C>T), rs352140 (C>T) and rs5743836 (A>G) also showed no significant difference between cancer and control groups (P>0.05).4. Stratified analysis was carried out on the cervical cancer group, the results showed that no statistical differences were found in the allele and genotype frequency of the rs352139, rs352140 and rs5743836 loci of TLR9 gene between in squamous carcinoma group and non-squamous carcinoma group,or between phase I and phase II,P > 0.05.However, the allele T in the promoter region of TLR9 gene was more frequent in the poorly differentiated group than the well-differentiated group, the difference was statistically significant (P=0.029,OR=0.629 95%CI= [0.414～0.957]).Interestingly, the distribution of allele C frequency in the site rs352139 were significantly different between the deep and shallow muscularis groups (P=0.038,χ2=4.299), among allele C appeared more frequently in the deep muscularis group than the shallow muscularis group (43.8%、32.7%). The distribution of allele and genotype frequency in the site rs352139 of the promoter region of TLR9 gene were statistically significant different between pelvic lymph node metastasis and no pelvic lymph node metastasis group(P=0.006,P=0.025), among which C/C of the appeared more frequently in the no pelvic lymph node metastasis groups than pelvic lymph node metastasis group (20.3% vs 4.7%).Conclusions:1.These three SNPs in the TLR9 gene promoter region may be not associated with the occurrence and development of cervical cancer in the Han population in Yunnan province.2.No statistically significant association was observed between polymorphisms in the site rs352139 of the promoter region of TLR9 gene with cervical cancer and precancerous lesions. And no obvious correlation was found when compared with different pathological type and clinical stage in cervical cancer cases. However, our study suggests that T allele is associated with cervical cancer tissue differentiation, the cervical cancer patients carried allele T may be most better tissue differentiation. At the same time, the C/T genotype was significantly more frequent in the deep muscularis group. The result suggests that C/T genotype may increase the risk of deep muscularis invasion in cervical cancer, it also prompts C/T genotype may be a risk factor associated with cervical cancer progress. This result may provide certain basis for cervical cancer treatment options and prognosis evaluation.In the comparison of pelvic lymph node metastasis,the cervical cancer patients carried allele T may be more metastasis,the C/C genotype was significantly more frequent in the no pelvic lymph node metastasis group.The result suggests that C/C genotype may reduce the risk of pelvic lymph node metastasis in cervical cancer.The results may provide certain genetic basis for cervical cancer treatment options and prognosis evaluation.3.No statistically significant association was observed between polymorphisms in the site rs352140 of the promoter region of TLR9 gene with cervical cancer and precancerous lesions. No significant correlation was found with the pathological type,clinical stage, tissue differentiation, muscular infiltration depth or lymph node metastasis for the polymorphisms studied.4.No statistically significant association was observed between polymorphisms in the site rs5743836 of the promoter region of TLR9 gene with cervical cancer and precancerous lesions. No association with pathological type,clinical stage, tissue differentiation, muscular infiltration depth or lymph node metastasis.