Associations between HLA Class I alleles and the prevalence of nasopharyngeal carcinoma (NPC) among Tunisians

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 p 2 -value = 0.0001 and = 0.003). Moreover, positive associations were observed for HLA-B-18, -B51 (split of -B5) and -B57 (p 2 -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; p 2 -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.

Association of MICA-129 polymorphism with nasopharyngeal cancer risk in a Tunisian population

“…Previous association studies showed that genetic background, especially that of HLA and MHCnon HLA loci, could exert an influence in NPC development [21][22][23]. A recent study of HLA class I diversity by sequence-based typing not only confirmed the earlier serologic findings but also identified a strong protective effect conferred by the HLA-B*1402-HLACw*0802 ancestral haplotype commonly found both in Tunisia and Morocco [24]. They also suggested that such association could be caused by the presence, within this haplotype, of a yet-to-beidentified tumor suppressor locus that may exert a dominant protective effect against the onset of NPC in North Africa.…”

Structural Basis for T Cell Alloreactivity among Three HLA-B14 and HLA-B27 Antigens

“…Nevertheless, the B*1402 subtype is widely distributed in various human populations, suggesting that the seemingly disadvantageous structural and biochemical features that are due to its unorthodox A pocket are no impediment for being a "successful" HLA class I antigen. However, the biological advantage conferred by expressing HLA-B14 molecules or of possessing HLA-B14-carrying haplotypes (63), if any, remains currently unclear.…”

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics

“…Nasopharyngeal carcinoma is an undiVerentiated neoplasm with marked lymphocytic inWltration that arises in the squamous epithelium overlying the nasopharyngeal lymphoid tissue. There is evidence suggesting that certain genotypes in HLA class I, TP53, and antigen processing genes inXuence susceptibility in North Africa (HadhriGuiga et al 2007;Hassen et al 2007;Li et al 2007b). …”