人乳头状瘤病毒感染及人白细胞抗原-DQB1等位基因多态性与南疆维吾尔族女性宫颈癌的关系

Association between HPV infection and HLA-DQB1 alleles polymorphism in the cervical carcinogenesis in Uyghur women in southern Xinjiang

目的 探讨人类乳头状瘤病毒（HPV）感染及人类白细胞抗原（HLA）-DQB1等位基因多态性与南疆维吾尔族女性宫颈癌的关系.方法 采用导流杂交基因芯片技术,检测190例南疆维吾尔族女性宫颈癌组织和190例正常维吾尔族女性宫颈组织21种HPV亚型的感染情况.采用聚合酶链反应序列特异性寡核苷酸探针（PCR-SSO）检测其5个HLA-DQB1等位基因的基因频率.结果 （1）在对照组中,HPV感染17例,感染率为8.9%.190例宫颈癌中,HPV感染133例,感染率为70.0%,高于对照组（P〈0.05）.其中HPV16的感染率最高,为64.7%,也明显高于对照组（3.7%,P〈0.05）.其他亚型的感染率均远低于HPV16,依次为HPV18（2.6%）、HPV68（2.1%）、HPV45（1.6%）、HPV58（1.6%）、HPV39（1.6%）、HPV31（1.1%）、HPV56（1.1%）及HPV59（0.5%）,中国汉族人常见类型HPV53和低危型HPV6的感染率均为0.5%.（2）宫颈癌组和对照组的HLA-DQBI＊03基因分布差异有统计学意义（P=0.014）,携带HLA-DQB1＊03基因者罹患宫颈癌的风险降低31.7%（OR=0.683）,其他等位基因与维吾尔族女性宫颈癌的发生无关.（3）携带HLA-DQB1＊06基因的宫颈癌患者HPV和HPV16的感染率高于非HLA-DQB1＊06携带者（P值分别为0.046和0.025）,携带HLA-DQB1＊06等位基因的维吾尔族女性更容易被HPV和HPV16感染（OR分别为1.808和1.879）.其他等位基因与HPV及HPV16感染无关.结论 南疆维吾尔族女性宫颈癌患者的HPV感染率高于非宫颈癌女性,均以HPV16感染为主.HLA-DQB1＊03可能为南疆维吾尔族女性罹患宫颈癌的保护基因.HLA-DQB1＊06为HPV和HPV16感染的易感基因.

Objective To investigate the association between HPV infection and HLA-DQB1 alleles polymorphism in the cervical carcinogenesis in Uyghur women in southern Xinjiang. Methods Twenty-one subtypes of HPV and the 5 alleles of HLA-DQB1 were detected from cervical tissues of 190 cervical cancer cases and 190 normal subjects by flow-through hybridization and gene chip （ HybriMax） assay and polymerase chain reaction sequence-specific oligonucleotide technique （ PCR-SSO）. Results （1） The positive rate of HPV in cervical cancer and control groups were 70. 0% and 8. 9% , respectively. HPV16 was the most common type in HPV positive cervical cancer patients with a rate of 64. 7% , followed by HPV18 （2.6%）, HPV68 （2. 1%）, HPV45 （1.6%）, HPV58 （1.6%）, HPV39 （1.6%）, HPV31 （1.1%）, HPV56 （1.1%）, HPV59 （0.5% ） , HPV53 （0.5% ） and HPV6 （0. 5% ）, respectively. The positive rates of HPV and HPV16 in the cervical cancer group were significantly higher than that in the control group. （2）The frequency of HLA-DQB1＊03 was significantly lower than that in the control group （OR = 0.683, 95% CI = 0.505-0.923）. The frequency of other HLA alleles had no significant differences between the cervical cancer group and the control group. （3） In the cervical cancer group, the frequency of HLA-DQB1＊06 in both HPV positive and HPV16 positive cases were significantly higher than that in both the HPV and HPV16 negative cases. Conclusion HPV16 is the most common type in both the cervical cancer and control groups. It appears that HLA-DQB1＊03 may be a protective gene in the cervical carcinogenesis in southern Xinjiang Uyghur women, and the HLA-DQB1＊06 is a susceptibility gene to HPV/HPV16 infection in Uyghur women. The study of HLA alleles in the cervical carcinogenesis in Uyghur women may play an important role in the intervention research of cervical cancer.