DESCRIPTION (provided by applicant): Nasopharyngeal carcinoma (NPC) occurs sporadically in the west but is endemic in southern China and Southeast Asia, with incidence rates from 15 to 50 per 100,000 This disease is far more prevalent in Cantonese speaking Guangdong regions than in other regions. Multiple studies suggest that both genetic and environmental factors including infection with Epstein-Barr Virus (EBV) and intake of preserved food containing nitrosamines and nitrite. Previously we carried out a family based linkage genome-scan analysis in a Cantonese speaking population in the Guangdong province and identified a susceptibility locus on chromosome 4p15.1-q12. We have been testing associations between biologically plausible candidate genes in the region on chromosome 4 and NPC risk. Recently we conducted a hospital-based NPC case- control study, aiming to test for associations between NPC and variants in Toll-like Receptor (TLR) 10, a gene has been implicated in cancer etiology in recent years, which locates between D4S3506 and D4S3503. Using an pre-existing 487 cases and 580 controls (frequency matched by age), we assessed each unique haplotype compared to the most common haplotype and we observed that the risk of developing NPC was significantly elevated among men who carried a haplotype of TLR10 "GCGTAAC" (P-value=0.00462). The haplotype "GCGTGGC" with frequency of 11.4% in TLR10 was found to be associated with NPC and this association. However, EBV infection status was not available for this pilot study. Here we proposing a new proposal which aims to 1) carrying out EBV antibody analysis for cases and controls using previously collected serum samples ; 2) reanalyze the variants in TLR10 including infection status of EBV in all individuals; 3) genotyping more TLR genes including TLR 1,6,9 and MYD88 and analyzing gene-gene interactions; we hypothesize that TLR genes are likely to interact with each other to create a joint effect to increase risk of developing NPC among individuals who have been infected with EBV. This study builds upon a long-term collaboration between Johns Hopkins University and the Cancer Center of Sun Yat-Sen University in Guangzhou, China. Potential findings will not only benefit the high risk population in China but also advance our understanding of the intriguing relationship among genetic factors, EBV infection and other environmental factors in causing EBV related cancers.
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