Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4

Abstract

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

An Update on Epstein-Barr Virus and Nasopharyngeal Carcinogenesis

“…These haplotypes include HLA A2-B46, HLA B17, HLA A2-B38, and HLA A2-B16 [24,25]. The genetic bases of familial NPC are not well understood, but susceptibility loci have been identified in chromosome regions 3p21 and 4p15 [26,27].…”

Mechanisms of cell immortalization mediated by EB viral activation of telomerase in nasopharyngeal carcinoma

“…Several factors have been identified in its aetiology in recent years, including infection of the Epstein-Barr virus (EBV), environmental risk factors and genetic susceptibility [1,2,5]. Of these aetiological factors, EBV infection appears to be the most important one [1][2][3][4]6].…”

The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation

“…Although the molecular basis of NPC development is still poorly elucidated, NPC pathogenesis has been shown to be strongly associated with Epstein-Barr virus (EBV), whether endemic or sporadic (Pathmanathan et al, 1995;Raab-Traub 2002). Consumption of salted fish in early childhood, tobacco smoking (Yu and Yuan 2002) and genetic predisposition (Lu et al, 1990;Feng et al, 2002;Xiong et al, 2004) have also been suggested as risk factors.…”