Selected class I and class IIHLA alleles and haplotypes and risk of high-grade cervical intraepithelial neoplasia
Selected class I and class IIHLA alleles and haplotypes and risk of high-grade cervical intraepithelial neoplasia
复制标题
DOI：
10.1002/ijc.23459
复制
发表时间：
2008-06-15
影响因子：
6.4
通讯作者：
Franco, Eduardo L.
中科院分区：
文献类型：
--
作者：
Ades, Steven;Koushik, Anita;Franco, Eduardo L.
人类白细胞抗原(HLAs)是免疫系统的外来抗原，可能是宫颈肿瘤的重要决定因素。先前发表的研究结果显示，人类白细胞抗原与宫颈肿瘤之间的关联有相当大的差异。宫颈癌风险生物标志物(BCCR)病例对照研究基于已发表文献中最一致的证据，阐述了特定的HLA等位基因作为辅助因素在高级别宫颈上皮内瘤变(HG-CIN)发生中的作用。病例(N=381例)为阴道镜检查确诊的HG-CIN患者，对照组(N=884例)为细胞学检查涂片正常的门诊妇女。受试者主要是法裔加拿大人。采用PGMY L1通用引物聚合酶链式反应和序列特异性引物聚合酶链式反应分别检测宫颈组织中人乳头瘤病毒(HPV)DNA和人类白细胞抗原(HL A)基因分型。与其他研究不同的是，DQB1*03和DRB1*13等位基因组与HG-CIN的风险无关。B7-DRB1*1501-DQB1*0602单倍型与HG-CIN风险降低41%相关(优势比[OR]=0.59；95%可信区间[CI]：0.36-0.96)，在HPV16或HPV18阳性受试者中，HG-CIN风险降低83%(OR=0.17；95%CI：0.05-0.54)。然而，矛盾的是，在对照组中，相同的单倍型与HPV16/18感染风险相关(OR=8.44，95%CI：1.12-63.73)。总之，B7-DRB1*1501-DQB1*0602单倍型对HG-CIN具有保护作用，尤其是在感染致癌HPV的个体中，但这种关联的机制似乎涉及HPV和CIN自然历史的多个步骤。(C)2008年Wiley-Liss，Inc.
Human leukocyte antigens (HLAs) present foreign antigens to the immune system and may be important determinants of cervical neoplasia. Previously published associations between HLA and cervical neoplasia exhibit considerable variation in findings. The biomarkers of cervical cancer risk (BCCR) case-control study addressed the role of specific HLA alleles as cofactors in the development of high-grade cervical intraepithelial neoplasia (HG-CIN) based on the most consistent evidence from published literature. Cases (N = 381) were women with histologically-confirmed HG-CIN attending colposcopy clinics and controls (N = 884) were women from outpatient clinics with normal cytological screening smears. Subjects were mainly of French-Canadian descent. Cervical specimens were tested for human papillomavirus (HPV) DNA and HLA genotypes by PGMY L1 consensus primer PCR and a PCR sequence-specific primer method, respectively. Unlike other studies, the DQB1*03 and DRB1*13 allele groups were not associated with risk of HG-CIN. The B7-DRB1*1501-DQB1*0602 haplotype was associated with a 41% overall reduction in HG-CIN risk (odds ratio [OR] = 0.59; 95% confidence interval [CI]: 0.36-0.96), and an 83% reduction in risk of HG-CIN among HPV 16 or HPV 18-positive subjects (OR = 0.17; 95%CI: 0.05-0.54). Paradoxically, however, the same haplotype was associated with HPV 16/18 infection risk among controls (OR = 8.44, 95%CI: 1.12-63.73). In conclusion, the B7-DRB1*1501-DQB1*0602 haplotype was protective against HG-CIN, especially in individuals infected with oncogenic HPV, but the mechanism of the association seems to involve multiple steps in the natural history of HPV and CIN. (C) 2008 Wiley-Liss, Inc.