Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc. NCI-Frederick, Frederick, MD 21702, USA.
Immunogenetics. 2010 Dec;62(11-12):761-5. doi: 10.1007/s00251-010-0477-5. Epub 2010 Sep 21.
Inherited genetic polymorphisms within immune response genes have been shown to associate with risk of invasive cervical cancer (ICC) and its immediate precursor, cervical intraepithelial neoplasia grade 3. Here, we used the transmission/disequilibrium test to detect disease-liability alleles and investigate haplotype transmission of KIR and HLA class I polymorphisms in a large family-based population of women with cervical cancer and their biological parents (359 trios). The effect of distinct human papillomavirus types was also explored. HLA-Cw group 1 (HLA-Cw alleles with asparagine at position 80), which serves as ligand for certain killer immunoglobulin-like receptors (KIR), was significantly overtransmitted in women with ICC (P = 0.04), and particularly in the subgroup of women infected with high risk HPV16 or 18 subtypes (P = 0.008). These data support the involvement of the HLA-C locus in modulating the risk of cervical neoplasia perhaps through its function as ligands for KIR, but functional studies are essential to confirm this hypothesis.
遗传免疫反应基因中的多态性已被证明与浸润性宫颈癌（ICC）及其直接前体宫颈上皮内瘤变 3 级（CIN3）的风险相关。在这里，我们使用传递/不平衡检验来检测与宫颈癌及其生物学父母（359 个三核苷酸）相关的疾病易感性等位基因，并研究杀伤细胞免疫球蛋白样受体（KIR）和 HLA Ⅰ类多态性的单倍型传递。还探讨了不同人乳头瘤病毒类型的影响。作为某些杀伤免疫球蛋白样受体（KIR）配体的 HLA-Cw 组 1（HLA-Cw 等位基因第 80 位为天门冬酰胺）在 ICC 妇女中明显过度传递（P=0.04），尤其是在感染高危 HPV16 或 18 亚型的妇女亚组中（P=0.008）。这些数据支持 HLA-C 基因座通过作为 KIR 的配体来调节宫颈癌前病变风险的参与，但是需要进行功能研究来证实这一假设。
