Association Between Genetic Variants In MiR-143/145 Flanking Sequences With Cervical Cancer In Yunnan Han Population

Aim:To investigate the effect of genetic variation in miR-143/145 flanking sequences on susceptibility to cervical cancer in Yunnan Han population.Method :In this study,242 patients and 249 controls were enrolled.The frequencies of rs17796757,rs353292,rs353293,rs4705342,and rs1723799 in the flanking sequence of miR-143 / 145 were studied by PCR-RFLP and snapshot.The expression of miR-143 / 145 in cervical cancer was detected by real-time quantitative PCR.The effect of rs353292 of miR-143 / 145 flanking sequence on transcriptional activity was analyzed by using dual-luciferase reporter gene detection system.To determine the type of body constitution and analyze the distribution of TCM constitution in cervical cancer patients according to the TCM body constitution classification judgment table.Result: The frequency of CT genotype of rs353292 C / T polymorphism in the cervical cancer group was 22.3%,higher than 15.3% in the control group(CT vs.CC: adjusted OR=1.63,95% CI,1.03-2.58,P=0.028;CC vs.CT/TT: adjusted OR= 1.65,95% CI,1.07-2.56,P=0.024).The frequency of CC genotype of rs4705342 C / T polymorphism in the cervical cancer group was 33.2%,higher than 15.7% in the control group(CC vs.TT:adjusted OR=2.88,95%CI,1.78-4.66,P<0.00;TT vs.CT/CC:adjusted OR=2.68,95%CI,1.73-4.14,P<0.001).The frequency of TC genotype of rs1723799 T / C polymorphism was47.9% in the cervical cancer group,which was lower than 61.5% in the control group(TCvs.CC: adjusted OR=0.42,95%CI,0.28-0.63,P<0.001).The rs17796757A/T,rs353293 A/G polymorphic were not statistically significant(P> 0.05).The frequency distribution of candidate loci was related to the clinical characteristics of cervical cancer.The expression of miR-143 / 145 was low in cervical cancer tissues.The expression of rs1723799 TC genotype was higher in miR-143/145(P=0.011,P=0.014),and rs4705342 CC genotype was lower in miR-145(P=0.011).In He La,HCT116,and A549 cell lines,the luciferase activity of rs353292 C / T allele T was significantly lower than that of C allele(P= 0.004,0.019,0.04).Among cervical cancer patients,damp heat constitution,yang deficiency constitution,and phlegm dampness constitution are the top three constitutions.Damp heat constitution is the most common constitution in patients younger than 50 years old,while phlegm dampness constitution and damp heat constitution are the most common constitution in patients older than 50 years old.Conclusion: The miR-143/145 flanking sequence rs353292,rs4705342,and rs1723799 may be associated with genetic susceptibility to cervical cancer.