HLA, HUMAN PAPILLOMAVIRUS AND INVASIVE CERVICAL CANCER

浸润性宫颈癌(ICC)的许多危险因素 描述：感染人乳头瘤病毒(HPV)，吸烟， 饮食不足，性伴侣多，刚开始时年龄较早 性交。最一致的危险因素是人类乳头瘤病毒。 感染，因为85%的宫颈肿瘤包含HPV DNA整合到 宫颈细胞的染色体。然而，HPV感染本身并不是 足以发展成宫颈癌。其他因素 一定是在做手术。最近，人类白细胞抗原的*03等位基因家族 据报道，DQ(Beta)1基因座在女性中的频率增加 被诊断为国际刑事法院。这代表了一个耐人寻味的联系，因为 DQ(Beta)1分子与病毒蛋白相互作用 T淋巴细胞的识别。DQ(Beta)1-HPV异常 相互作用可能导致免疫机制的激活有缺陷 控制HPV感染的上皮细胞恶变的研究 细胞。此外，影响癌基因激活的基因变化(S) 甚至某些肿瘤抑制基因的失活或突变也必须 参与宫颈癌的发展。 这项研究计划将对200名患有人类白细胞抗原和人乳头状瘤病毒的女性进行特征分析。 经病理证实为ICC。将输入人类白细胞抗原DQ(Beta)1基因座 应用聚合酶链式反应(PCR)检测患者及其父母 外显子2的扩增和测序。非传递亲本 等位基因将被用来构建种族匹配的对照样本。人类乳头瘤病毒 通过聚合酶链式反应扩增从肿瘤活检组织中鉴定出基因类型 L1开放阅读框与限制性片段长度多态性 (RFLP)分析。将在人类白细胞抗原上测试等位基因之间的关联性 人乳头瘤病毒DQ(Beta)1基因座与高危基因分型 宫颈癌是妇科常见的恶性肿瘤之一。现在还早着呢 通过识别遗传因素进行检测可以大大提高 我们对疾病机制的理解以及加强预防 努力。此外，这些遗传因素还可以用于未来 通过容易接近的宫颈阴道脱落进行人群筛查 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.