HLA, HUMAN PAPILLOMAVIRUS AND INVASIVE CERVICAL CANCER

浸润性宫颈癌（ICC）的一些风险因素已经被发现。 描述：人乳头瘤病毒（HPV）感染，吸烟， 饮食不足，多个性伴侣，以及最初的年龄 性交 最一致的危险因素是人乳头瘤病毒 85%的宫颈肿瘤含有HPV DNA， 子宫颈细胞的染色体。 然而，HPV感染本身并不是 子宫颈癌的早期症状 附加因素 一定在运作。 最近，HLA上的 *03等位基因家族 DQ（β）1位点在女性中的频率增加 诊断为ICC。 这代表了一个有趣的关联，因为 DQ（β）1分子与病毒蛋白相互作用，以促进其 T淋巴细胞识别。 DQ（Beta）1-HPV中的抗体 相互作用可能导致免疫机制激活缺陷 控制HPV感染的上皮细胞恶性转化 细胞 此外，影响癌基因激活的遗传变化 甚至某些肿瘤抑制基因的失活或突变， 宫颈癌的早期症状有哪些？ 这项研究计划将在200名女性中描述HLA和HPV的特征， 病理证实的ICC。 HLA DQ（Beta）1基因座将在 患者及其父母使用聚合酶链反应（PCR） 外显子2的扩增和测序。 非遗传性父母 等位基因将用于构建种族匹配的对照样品。 HPV 基因型将通过PCR扩增从肿瘤活检中鉴定， L1开放阅读框和限制性片段长度多态性 （RFLP）分析。 将检测HLA等位基因之间的关联 DQ（Beta）1基因座与HPV高危基因型 宫颈癌是一种常见的妇科恶性肿瘤。 其早期 通过识别遗传因素进行检测可以大大提高 我们对疾病机制的了解以及加强预防 努力 此外，这些遗传因素可以用于未来的研究。 通过容易获得的宫颈阴道脱落物进行人群筛查 细胞

A number of risk factors for invasive cervical cancer (ICC) have been described: infection by human papillomavirus (HPV), cigarette smoking, dietary deficiencies, multiple sexual partners, and early age at first intercourse. The most consistent risk factor is human papillomavirus infection as 85% of cervical tumors contain HPV DNA integrated into the chromosomes of the cervical cells. However, HPV infection alone is not sufficient for the development of cervical cancer. Additional factors must be operating. Recently, the *03 family of alleles at the HLA DQ(Beta)1 locus have been reported at increased frequency among women diagnosed with ICC. This represents an intriguing association, since the DQ(Beta)1 molecule interacts with viral proteins to facilitate their recognition by T lymphocytes. Abnormalities in the DQ(Beta)1-HPV interaction may result in a defective activation of immune mechanisms that control the malignant transformation of HPV-infected epithelial cells. In addition, genetic changes affecting activation of oncogene(s) and even inactivation or mutation of certain tumor suppressor genes must be involved in the development of cervical cancer. This research proposal will characterize HLA and HPV in 200 women with pathologically confirmed ICC. The HLA DQ(Beta)1 locus will be typed in patients and their parents using polymerase chain reaction (PCR) amplification and sequencing of exon 2. The nontransmitted parental alleles will be used to construct an ethnic-matched control sample. HPV genotypes will be identified from tumor biopsies by PCR amplification of the L1 open reading frame and restriction fragment length polymorphism (RFLP) analysis. Associations will be tested between alleles at the HLA DQ(Beta)1 locus and high risk genotypes of HPV. Cervical cancer is a highly prevalent gynecologic malignancy. Its early detection through identification of genetic factors can greatly improve our understanding of disease mechanisms as well as enhance preventive efforts. In addition, these genetic factors can be used for future population screening through easily accessible exfoliated cervicovaginal cells.