Back to Search
Start Over
A GWAS meta-analysis and replication study identifies a novel locus within CLPTM1L/TERT associated with nasopharyngeal carcinoma in individuals of Chinese ancestry
- Publication Year :
- 2015
-
Abstract
- 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. Cancer Epidemiol Biomarkers Prev; 25(1); 188–92. ©2015 AACR.
- Subjects :
- 0301 basic medicine
Epidemiology
Nasopharyngeal neoplasm
Single-nucleotide polymorphism
Genome-wide association study
Locus (genetics)
Biology
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
0302 clinical medicine
Asian People
CDKN2A
medicine
Humans
Genetic Predisposition to Disease
Gene
Telomerase
Genetics
Nasopharyngeal Carcinoma
Haplotype
Carcinoma
Membrane Proteins
Nasopharyngeal Neoplasms
medicine.disease
Prognosis
Neoplasm Proteins
030104 developmental biology
Oncology
Nasopharyngeal carcinoma
Haplotypes
Genetic Loci
030220 oncology & carcinogenesis
Case-Control Studies
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....10d2536f5e926de655262ff944fab4ba