Association of polymorphic extracellular domains of MICA with cervical cancer in northeastern Thai population

Abstract

Cancer of the cervix is one of the common cancers among women worldwide. The primary risk factor of cervical cancer is the high-risk group human papillomavirus infection. Host genetic factors should also be involved. Major histocompatibility complex class I chain related A (MICA), a ligand to the natural killer cell receptor group (NKG)2D receptor relevant to immune surveillance, was investigated as a potential candidate. MICA is highly polymorphic. Although the data were limited regarding functional polymorphism, it is conceivable that polymorphism of MICA may contribute to different degree of immune activation caused by different NKG2D-binding affinity, acting as a susceptible factor for development of cervical cancer. In this study, we have developed a polymerase chain reaction-sequence-specific primer technique defining most of MICA alleles with a total of 41 primer mixes. This set of primers could especially discriminate MICA*045 (formerly 052), a common allele in northeastern Thai population, from MICA*00701, a common allele in Caucasian population. Based on the distribution of MICA in northeastern Thai population, only 27 primer mixes were required to screen the MICA polymorphisms in this population. This set of primers was used for MICA typing of 100 samples of cervical cancer compared with 94 samples of healthy northeastern Thai females (NETF). Thirteen alleles or groups of alleles were identified in these samples. Common alleles in our population were MICA*00801(027,048)/0803, MICA*010 and MICA*00201(020, 023, 050)/30/41. Statistically significant differences were not observed in the distributions of MICA alleles between different stages of patients and the control group. However, there were particular residues that were negatively associated with cervical cancer, suggesting active MICA motifs in immune activation. © 2007 Blackwell Munksgaard.