Association Between Polymorphisms In TLR4 And CDK6 Genes Targeted By MicroRNA And Pre-cervical Cancer

ObjectiveCervical cancer, the third most common cancer among females, is still a important public health problem worldwide. It has established that high-risk HPV was a necessary but not a sufficient factor of cervical cancer. Micro-RNA can regulate lots of important genes involving in the progress of cervical cancer. The aim of this study was to investigate the association between SNPs in micro RNA target sites of TLR4 gene and CDK6 gene and pre-cervical cancer in south Han population of China. Also, potential risk factors of pre-cervical cancer were evaluated with the aim of providing further rich molecular mechanisms for the etiology and prevention strategies of cervical cancer.Methods1. A matching case-control study was adopted. A total of 592 subjects were included in the study, with 296 subjects with pre-cervical cancer and 296 healthy subjects. 5ml peripheral whole blood was collected for obtaining genomic DNA.2. All personal information and potential risk factors was collected with questionnaire.3. Exfoliated cell of cervix was collected for HPV genotype analyse and TCT test. SNPs genotyping was obtained by utilizing the Sequenom Mass ARRAY i PLEX platform.4. Statistical Product and Service Solutions software 13.0 was used to estimate the associations between the analyzed the polymorphisms within micro RNA target sites of TLR4 and CDK6 gene and pre-cervical cancer.Results1. A total of 7 SNPs in the two genes was detected, including TLR4 gene(rs11536896 and rs7873784), CDK6 gene(rs42035, rs42033, rs42377, rs4272 和 rs8179).2. There were no significant differences in the associations between 7 SNPs and pre-cervical cancer after adjusting the risk factors(passive smoking, age at menarche, age at first sexual life, times of pregnancy, high-risk HPV infection, number of high-risk HPV infected) in logistic regression model.3. There were no significant differences in TLR4 and CDK6 genes haplotypes between pre-cervical cancer patients and control subjects.4. 7 SNPs were interacted with high-risk HPV in the progress of pre-cervical cancer. However, after adjusting the risk factors(passive smoking, age at menarche, age at first sexual life, times of pregnancy, high-risk HPV infection, and number of high-risk HPV infected), there was no significant differences.5. High-risk HPV infection, age at menarche more than 16 years, age at first pregnancy less than 21 years were particular risk factors for pre-cervical cancer in our studied population. ConclusionsOur results indicate that polymorphisms within micro RNA target sites of TLR4 and CDK6 genes may not be associated with genetic susceptibility of pre-cervical cancer, and may there is no interaction between these SNPs and high-risk HPV infection contributing to the progress of pre-cervical cancer.