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http://purl.uniprot.org/citations/26545403http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26545403http://www.w3.org/2000/01/rdf-schema#comment"

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). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three 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).

Conclusions

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 has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity.

Impact

Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.org/dc/terms/identifier"doi:10.1158/1055-9965.epi-15-0144"xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Chen C.J."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Cui Q."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Chen M.Y."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Zhang H."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Zeng Y.X."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Yu K."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Ng C.C."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Liu J.J."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Liu W.S."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"McKay J.D."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Chang Y.S."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Zhou G.Q."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Chen L.Z."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Bei J.X."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Hildesheim A."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Teo S.H."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Guo Y.M."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Jia W.H."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Hsu W.L."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Khoo A.S."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Feng F.T."xsd:string
http://purl.uniprot.org/citations/26545403http://purl.uniprot.org/core/author"Feng Q.S."xsd:string