Association of HLA-G polymorphisms with nasopharyngeal carcinoma risk and clinical outcome Nahla Ghandri a , Sallouha Gabbouj a , Karim Farhat a , Noureddine Bouaouina a,b , Hamdi Abdelaziz c , Abdelatif Nouri d , Lotfi Chouchane a,e , Elham Hassen a * a Molecular Immuno-oncology Laboratory, Faculty of Medicine of Monastir, Tunisia b Department of Cancerology and Radiotherapy, CHU Farhat Hached, Sousse, Tunisia c Department of Surgery, Fattouma Bourguiba Hospital, Monastir, Tunisia d Department of Pediatric Surgery, Fattouma Bourguiba Hospital, Monastir, Tunisia e Department of Genetic Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar ARTICLE INFO Article history: Received 17 June 2010 Accepted 5 October 2010 Available online 20 October 2010 Keywords: HLA-G Nasopharyngeal carcinoma Susceptibility Survival ABSTRACT The expression of human leukocyte antigen–G (HLA-G) in tumor cells may facilitate the escape of the tumor from immunosurveillance; thus the aim of this study was to evaluate the influence of HLA-G polymorphisms occurrence on nasopharyngeal carcinoma (NPC) susceptibility, severity, and survival. Using the restriction fragment length polymorphism–polymerase chain reaction and the amplification refractory mutation system–polymerase chain reaction method, 186 Tunisian patients and 189 healthy controls were genotyped for nonsynonymous polymorphisms in HLA-G codon 31Thr/Ser, codon 110Leu/Ile and codon 130Leu/fram- shift. When allele, genotype and haplotype frequencies between patients and controls were compared for each single nucleotide polymorphisms (SNP), no statistical significant differences were observed. According to the lymph node status and the tumor stages, the Ile110 allele was shown to be significantly less frequent among patients with a positive lymph node status and more severe tumor stages (stage I–II vs III–IV), respectively. Moreover, the codon 130C deletion occurrence was significantly associated with a decreased NPC free disease and overall survival. Altogether our results suggest a possible role for HLA-G locus in NPC progression and aggressiveness.  2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells of the nasopharynx. Compared with other head and neck cancers, NPC exhibits very different features, such as its spe- cific geographic incidence and its multifactorial etiology [1]. NPC is rare in most parts of the world (2/100,000 inhabitants) but is common in some geographic areas. The rates are high to interme- diate in some areas of southeastern China, southern Asia, and northern Africa (from 7–25/100,000 inhabitants) [2]. NPC demon- strates a bimodal age distribution in some populations, such as the North African and the North American populations, with peaks at ages 10 –20 years and 40 – 60 years [3,4]. NPC pathogenesis is com- plex; the etiologic factors include genetic susceptibility, chemical carcinogens, and association with Epstein–Barr virus infection [5]. Since 1975, numerous studies have indicated that specific hu- man leukocyte antigen (HLA) haplotypes and genes within the HLA complex are associated with NPC [6]. Today, progress in NPC ge- netic analysis has allowed the description of a large number of genetic associations between the HLA– class I region and NPC oc- currence [7]. Whatever the NPC incidence area, HLA genes are associated with NPC; but because of population-dependent HLA distributions, HLA susceptibility alleles to NPC vary markedly be- tween ethnic groups. Direct sequencing of the HLA-class I genes showed positive associations for HLA-B18, -B51 and -B57 with NPC risk in Tunisians and allowed the identification of a rare haplotype (HLA-B*14:02/Cw*08:02) in patients with NPC [8]. However, Tang et al, recently showed that among a Southern Chinese population the HLA-A*02:06 and HLA-B*38:02 alleles and the A*02:07/B*46:01 and the A*33:03/B*58:01 haplotypes were associated with high NPC risk [9]. The exact role of HLA– class I alleles in NPC pathogen- esis is still undetermined. One explanation of the HLA/NPC rela- tionship is that the associated alleles are in linkage disequilibrium with a gene or genes the functions of which favor NPC occurrence and/or progression. Numerous non-HLA gene polymorphisms lo- cated nearby or within the HLA– class I loci were also found to be associated with NPC, including TAP-1, MHC class I chain–related A (MICA), heat shock protein, and the nonclassical class I HLA-E genes [7,10]. However, to date, no information regarding the implication of the HLA-G gene polymorphisms in NPC risk has been available in the literature. * Corresponding author. E-mail address: elham.hassen@isbm.rnu.tn (E. Hassen). Human Immunology 72 (2011) 150 –158 Contents lists available at ScienceDirect 0198-8859/11/$32.00 - see front matter  2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.humimm.2010.10.006