Abstract
The high prevalence of nasopharyngeal cancer (NPC) in Southern Asia and Mediterranean Northern Africa suggests genetic predisposition among other factors. While Human Leukocyte Antigen (HLA) haplotypes have been conclusively associated with NPC predisposition in Asians, Northern African Maghrebians have been less intensely studied. However, low resolution serological methods identified weak positive associations with HLA-B5, B13 and B18 and a negative with HLA-B14. Using sequence based typing (SBT), we performed a direct comparison of HLA class I frequencies in a cohort of 136 Tunisian patients with NPC matched for gender, age and geographical residence to 148 normal Tunisians. The bimodal age distribution of NPC in Maghrebians was also taken into account. HLA frequencies in normal Tunisians were also compared with those of Northern Moroccan Berbers (ME) to evaluate whether the Tunisian population in this study could be considered representative of other Maghrebian populations. HLA-B14 and -Cw08 were negatively associated with NPC (odd ratio = 0.09 and 0.18 respectively, Fisher p2-value = 0.0001 and = 0.003). Moreover, positive associations were observed for HLA-B-18, -B51 (split of -B5) and -B57 (p2-value < 0.025 in all) confirming previous findings in Maghrebs. The HLA-B14/Cw*08 haplotype frequency (HF) was 0.007 in NPC patients compared to 0.057 in both Tunisian (OR = 0.12; p2-value = 0.001) and Moroccan controls. This study confirms several previous associations noted by serologic typing between HLA class I alleles and the prevalence of NPC in Maghrebians populations. In addition, we identified a putative haplotype rare in Tunisian patients with NPC that may serve as a genetic marker for further susceptibility studies.
Highlights
The prevalence of Epstein-Barr virus (EBV)-associated anaplastic nasopharyngeal carcinoma (NPC) might be partially dependent upon genetic background affecting predominantly certain ethnic groups1
Some regions of Southern Asia suffer about a 100-fold higher prevalence compared with populations not at risk and this high prevalence is maintained upon immigration to Western Countries such as in the U.S Chinese population Northern African populations (Algerians, Moroccans and Tunisians) referred to as Maghrebians suffer increased prevalence of NPC which persists upon migration to low risk areas [1,2] heterogeneity of viral strains, dietary, environmental and socio-economical variables have been implicated as predisposing factors, it is likely that genetic traits play a significant role at least in Asians [3,4]
Many case-control studies pointed at Human Leukocyte Antigen (HLA) class I as a genomic region strongly associated with the prevalence of NPC in Southern Chinese [5,6,7,8,9,10,11,12,47,48,49] Such associations may bear two possible explanations; first the antigen presenting function of HLA molecules may be responsible for an altered effectiveness of the immune response against tumor associated antigens expressed by NPC in individuals bearing different HLA alleles [10]
Summary
The prevalence of Epstein-Barr virus (EBV)-associated anaplastic nasopharyngeal carcinoma (NPC) might be partially dependent upon genetic background affecting predominantly certain ethnic groups. The HLA-A2 serologic family includes about 100 alleles [15] whose distribution is different among ethnic groups with HLA-A*0201 (~90%) and HLA-A*0205 (~5%) predominant among Caucasian and HLA-A*0203 (~20%) -A*0206 (~15%) and -A*0207 (~40%) in Asians [16,17,18,19] Interestingly, sequence based typing (SBT) in Taiwanese identified a positive association between HLA-A*0207 (but not other HLA-A2 subtypes) and NPC [10]. This association was strong when the observation was extended to the HLA-A*0207/ B*4601 haplotype. Chromosome 6p, in particular 6p21-23, is characterized by unusually high gene density harboring gene clusters coding for several protein families besides HLA molecules [20], it remains unclear whether NPC/HLA associations reflect distinct antigen presentation potentials of various alleles or rather represent a marker for a susceptibility/protection locus in strong linkage disequilibrium with the HLA region [21]
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