HPV16变异体在新疆地区宫颈癌及癌前病变中的分布研究

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目的:研究新疆地区HPV16 E6、E7、LCR基因突变情况,分析HPV16变异体在宫颈癌及癌前病变发生发展中的作用。方法:选择HPV16阳性的宫颈癌及癌前病变患者,提取基因组DNA,利用PCR扩增HPV16 DNA E6、E7基因及LCR区核苷酸片段,正反向测序。与HPV16基因序列分析比对,分析核苷酸突变位点。结果:E6基因突变率为80.00%(92/115)主要突变位点T350G(59.78%)、T178G(18.47%);E7突变率为54.78%(63/115),主要突变位点A647G(33.33%)、T846C(26.98%);LCR突变率为23.48%(27/115),主要突变位点为C24T(74.07%)、C13T(25.92%)。维吾尔族T350G突变率较汉族妇女显著升高,而汉族A647G、T846C、C24T突变率显著高于维吾尔族,差异具有统计学意义(P<0.05)。维吾尔族宫颈癌组T350G突变率显著高于炎症组(P<0.05),且随病变严重程度增加突变率上升,汉族T350G、A647G、T846C、C24T突变率炎症组、宫颈病变组显著高于宫颈癌组(P<0.05),维吾尔族C24T突变率炎症组显著高于宫颈癌组(P<0.05),差异均具有统计学意义(P<0.05)。结论:HPV16E6、E7突变可能与宫颈病变进展有关,T350G突变可能是维吾尔族宫颈癌高发的原因之一。 Objective: To study the mutations of HPV16 E6, E7 and LCR genes in Xinjiang and to analyze the role of HPV16 variants in the development of cervical cancer and precancerous lesions. Methods: Genomic DNA was extracted from patients with HPV16-positive cervical cancer and precancerous lesions. HPV16 DNA E6, E7 and LCR regions were amplified by PCR and sequenced. Compared with HPV16 gene sequence analysis, nucleotide mutation sites were analyzed. Results: The frequency of mutation of E6 gene was (T350G) (59.78%) and T178G (18.47%) in 80.00% (92/115), the positive rate of E7 mutation was 54.78% (63/115), the major mutation was A647G (33.33% ), T846C (26.98%). The mutation rate of LCR was 23.48% (27/115). The main mutation sites were C24T (74.07%) and C13T (25.92%). The mutation rate of T350G in Uighur was significantly higher than that in Han women, while the mutation rates of A647G, T846C and C24T in Han were significantly higher than those in Uighur (P <0.05). The mutation rate of T350G in Uigur cervical cancer group was significantly higher than that in inflammation group (P <0.05), and the mutation rate increased with the severity of disease. The frequencies of T350G, A647G, T846C and C24T mutation in inflammatory group and cervical lesion group were significantly higher than those in cervical cancer group Group (P <0.05). The Uygur C24T mutation rate in inflammation group was significantly higher than that in cervical cancer group (P <0.05), the differences were statistically significant (P <0.05). Conclusion: The mutations of HPV16E6 and E7 may be related to the progression of cervical lesions. The mutation of T350G may be one of the reasons for the high incidence of cervical cancer in Uighur.
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