A GWAS meta-analysis and replication study identifies a novel locus within CLPTM1L/TERT associated with nasopharyngeal carcinoma in individuals of Chinese ancestry
A partir de données de 4 études d'association sur le génome entier menées en population d'origine chinoise (2 152 cas, 3 740 témoins), cette méta-analyse identifie un nouveau locus sur la région chromosomique CLPTM1L/TERT en association avec le risque de carcinome du rhinopharynx
Background: Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. Methods: We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases;3,740 controls). 43 noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of 4 independent case-control studies across 3 regions in Asia (4,716 cases;5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. Results: In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR=0.81;p-value 6.3*10-13). Our results also provide support for associations reported from published NPC GWAS - rs6774494 (p = 1.5*10-12;located in the MECOM gene region), rs9510787 (p = 5.0*10-10;located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (p = 2.8*10-8,p = 7.0*10-7,and p = 8.4*10-7 respectively;located in the CDKN2A/B gene region). Conclusion: We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene is important for telomere maintenance and has been reported to be over-expressed in NPC, and an EBV protein expressed in NPC (LMP1) modulates TERT expression/telomerase activity. Impact: Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis.