Further evidence for an HLA-related recessive mutation in nasopharyngeal carcinoma among the Chinese

Abstract

We typed 247 cases of nasopharyngeal carcinoma (NPC), a disease predominantly of the southern Chinese, and 274 controls from the Chao Shan region of China's Guangdong province for HLA A and B. Besides confirming the established associations with A2, A33, B46 and B58 (positive associations) and A11 (negative association), the results demonstrated a number of rarer alleles with strong negative association with NPC. Our data, combined with those from the previous studies in Southern Chinese, displayed the protective effects for A31 (odds ratio (OR) ¼ 0.0; 95% confidence interval (CI) ¼ 0 -0.11), B13 (OR ¼ 0.50; 95% CI ¼ 0.35 -0.69), B27 (OR ¼ 0.49; 95% CI ¼ 0.25 -0.92), B39 (OR ¼ 0.18; 95% CI ¼ 0.06 -0.48) and B55 (OR ¼ 0.32; 95% CI ¼ 0.14 -0.68), the ORs comparing individuals with or without each allele. Other ethnic groups do not display such large HLA-associated variation in NPC risk. We show that a linked NPC gene with dominant mode of action could not generate such large protective effects. The results provide strong supporting evidence for the existence of a southern Chinese specific, recessive NPC gene closely linked to the HLA region as a major determinant of the Chinese risk for the disease.

Genetic link between Chaoshan and other Chinese Han populations: Evidence from HLA‐A and HLA‐B allele frequency distribution

“…However, the distribution of the negatively associated alleles and haplotypes followed a ''two-way'' pattern. Among them, A*11, B*27, and B*55, and their associated haplotypes A*11-B*60, A*11-B46, A*11-B*75, and A*11-B*27 were more common in southern Chinese than in northern Chinese, whereas A*31 and B*13, two alleles with strong protective effects for NPC (Hu et al, 2005), were predominantly high in northern Chinese. High frequency of protective alleles and haplotypes in southern Chinese may reflect selective advantage of human genome against NPC similar to certain human genetic variants occurred in countries in the malaria belt, which have protective effects against fatal malaria complications (Ayi et al, 2004;Cockburn et al, 2004;Mockenhaupt et al, 2004;Williams et al, 2005).…”

“…For example, nasopharyngeal carcinoma (NPC) is prevalent among southern Chinese and those originating from southern China, but rarely seen in northern China (Parkin et al, 2002). It has been found that the HLA alleles A*02, A*33, B*38, B*46, and B*58 and the associated haplotypes A*02-B*46 and A*33-B*58 confer increased risk for NPC, whereas A*11, A*31, B*13, B*27, B*39, and B*55 are negatively associated with the disease (Simons et al, 1975;Chan et al, 1983;Hildesheim et al, 2002;Lu et al, 2003;Hu et al, 2005). Interestingly, our study showed that the alleles and haplotypes associated (positively or negatively) with NPC displayed the distinctive distribution patterns between northern and southern Chinese (Tables 4 and 5).…”

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].…”

Oropharyngeal Cancer, Race, and the Human Papillomavirus

“…One case-control study of nasopharyngeal carcinoma (with age-and geography-matched controls) showed that having a first-degree relative with nasopharyngeal carcinoma increases the risk of this disease by 7.6-fold (22). Nasopharyngeal carcinoma is associated with certain human leukocyte antigen haplotypes, which also could explain a genetic predisposition, at least in some populations (4,23).…”