High Risk Factors Of Squamous Cervical Cancer And Cervical Intraepithelial Neoplasia And Correlation To Aromatase P450, Estrogen Receptor β And Cytochrome P1A1Genetic Polymorphisms

Objective:1) The clinical data in the patients of squamous cervical cancer (SCC) and cervical intraepithelial neoplasia (CIN) was analyzed and studied preliminarily, to discuss the related risk factors of SCC and CIN, to look for its high-risk groups. It may provide some clinical evidence to made prevention and control measures about SCC and CIN.2) We studied and analyzed cytochrome P1A1(CYP1A1) genetic polymorphisms, the expression of aromatase P450(P450arom) and estrogen receptor (3(ER-P) of cervical lesions tissue, in order to understand the role of CYP1A1genetic polymorphisms, P450arom and ER-P in the development of SCC and CIN, and to discover whether there was a difference of CYP1A1genetic polymorphisms, P450arom and ER-Pin the patients undergoing SCC and CIN between Uygur and han nationality of Xinjiang.3) In order to investigate the role of high-risk human papilloma virus (HR-HPV) load in predicting the development and monitoring prognosis of SCC and CIN, the correlation study between HR-HPV load and pathogenesis of cervical lesions was analyzed, and the patients enrolled in this study were followed up as well. Methods:1) Using the form of clinical epidemiological questionnaire, gynecologic and laboratory examination, we carried out clinical epidemiological investigation, gynecologic examination and HC2-HPV-DNA testing for195cases of patients which covers119cases of CIN,76cases of SCC,127cases of the control people (cervical cytology negative) in our hospital medical center during the same period. The risk factors of SCC and CIN were analyzed by non-conditional logistic regression and OR value and95%CI were calculated. Correlative analysis between HR-HPV loading and the grade of cervical lesions was made.2) Peripheral venous blood among the outpatients and inpatients with SCC and CIN, the control people from Xinjiang tumor hospital, were characterized by PCR-RFLP to investigate CYP1A1genomic diversity, the difference of the different grade of cervical lesions and the difference between between Uygur and Han ethnic group in Xinjiang.3) The expression of P450arom and ER-β in60SCC specimens,60CIN specimens and60adjacent normal cervical tissues were examined using immunohistochemical method(S-P) to investigate the difference of the different grade of cervical lesions and the difference between between Uygur and han nationality of Xinjiang.4) Follow up analysis of the association between HR-HPV load and the prognosis in119patients with CIN and76patients with SCC, follow-up period from31months to54months. Results:1) HR-HPV load is significantly different (P=0.000) among the patients with SCC, CIN and the control group. The result shows positive correlation between HR-HPV load and the histologic grade of cervical lesions.2) The distribution of CYP1A1gene Msp I polymorphism was significantly different (P=0.038) in three groups (SCC, CIN and control group). The patient with C genotype (homozygous mutations) had higher likelihood to fill in CIN., however,there was not different Msp I loci genotype distribution between Uyghur and Han ethnic group.3) The expression of P450arom was lower in mormal cervical tissues (17.9%,10/56) than CIN and SCC(P=0.001). The expression of P450arom was55%(33/60) in SCC tissues, while48%(24/50) in CIN tissue (P=0.765). The expression of ER-βwas57.9%(33/57) in normal cervical tissue, while37.3%(19/51) in CIN and15.3%(9/59) in SCC, Decreasing expression trend of ER-βwas shown with increasing histologic grading in cervical lesions (P=0.000).4) Sustained HR-HPV infection is high risk factor of postoperative relapse in follow up VAIN and CIN patients. Conclusions:1) The HR-HPV HPV load was positively correlated with the occurrence of SCC and CIN.2) The people with C genotype (homozygous mutations) was susceptible to CIN. But there is no significant Msp1loci genotype distribution differences of CYP1A1between Uygur and Han Ethnic group in Xinjiang.3) Increasing exposure to endogenous estrogen by cervical local cells and sensitivity of cervical cells to estrogen may lead to promoter squamous carcinogenesis.4) The persistent infected of HR-HPV in vagina was the high-risk factor of VAIN and CIN after SCC and CIN treatment.