title: 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.
authors.affiliation: Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Lixin2@cc.nih.gov
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Nahla
authors.initials: N
authors.lastname: Ghandri
authors.forename: Daniela
authors.initials: D
authors.lastname: Piancatelli
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: Deborah
authors.initials: D
authors.lastname: Chen
authors.forename: Fu-Meei
authors.initials: FM
authors.lastname: Robbins
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Alessandro
authors.initials: A
authors.lastname: Monaco
authors.forename: Silvia
authors.initials: S
authors.lastname: Selleri
authors.forename: Noureddine
authors.initials: N
authors.lastname: Bouaouina
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
authors.forename: Domenico
authors.initials: D
authors.lastname: Adorno
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
mesh_terms: D000328:Adult; D017677:Age Distribution; D000483:Alleles; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006262:Health; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D015995:Prevalence; D014416:Tunisia / Q000453:epidemiology
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I