The association between haplotype of PIGR and genetic susceptibility of nasopharyngeal carcinogenesis

Abstract

Nasopharyngeal carcinoma (NPC) is a rare tumor in the Western world but occurs at high frequency in South China and Southeast Asia including Thailand. Emigrant Chinese population in several countries showed a higher incidence of NPC than the indigenous population. Moreover, numerous factors have been associated with the risk of NPC. To begin with genetics of the host also play a major role for NPC development. For example, unique alleles of human leukocyte antigen (HLA) and cytochrome P4502E1 (CYP2E1) showed the association with high relative from several Asia ethnic groups and Chinese in Taiwan, respectively. In addition, several reports regarding environmental factor indicated that consuming of salty fishes or preserved food with high concentration of chemical carcinogen such as nitrosamine, promoted the development of NPC. Finally, Epstein-Barr virus (EBV) was the most important factor to initiate NPC development Many reports suggested that specific receptor for EBV infected into B cell was complement receptor type 2(CR2). However, mechanism of EBV how to infect epithelium cell was not completely understood. To clarify how EBV enter into human cell, genetic susceptibility of candidate nasopharyngeal epithelium receptor was suggested. Our previous study reported on the association between NPC and polymeric immunoglobulin receptor (PIGR) intron polymorphism. Thus, PIGR was hypothesized to function as the receptor. To prove the hypothesis, the study was investigated PIGR SNPs in 222 cases and 368 controls, divided into Thai, Chinese and Thai-Chinese ethnic origins. The result indicated that PIGR was an NPC susceptible gene. The associated risk of each ethnic group was detected with high precision by PIGR1739C→T, and the significant OR (95%CI), 2.04 (1.62-2.58) between the two alleles of all cases of these three groups, was revealing, p < 0.00000001. The affect of PIGR1739C was similar to that of autosomal recessive gene, in which two homozygous alleles, but not heterozygous, were required to increase the relative risk, OR (95%CI) = 2.52 (1.91-3.31). Haplotype analysis of the two missense PIGRSNPs.1093G→A and 1739 C→T, not only confirmed the role of PIGR1739C→T, but also suggested the function of 1093G→A within 1739T subset. In conclusion, is substantial genetic evidences to support that plgR serves as EBV nasopharyngeal epithelium receptor via the failure of lgA-EBV complex transcytosis. In addition, variants of PIGR could alter susceptibility of people from endemic areas to develop NPC