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A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry

Bei JX 1 , Su WH 2 , Ng CC 3 , Yu K 4 , Chin YM 3 , Lou PJ 5 Show all authors , Hsu WL 6 , McKay JD 7 , Chen CJ 6 , Chang YS 8 , Chen LZ 1 , Chen MY 1 , Cui Q 1 , Feng FT 1 , Feng QS 1 , Guo YM 1 , Jia WH 1 , Khoo AS 9 , Liu WS 1 , Mo HY 1 , Pua KC 10 , Teo SH 11 , Tse KP 8 , Xia YF 1 , Zhang H 12 , Zhou GQ 12 , Liu JJ 13 , Zeng YX 1 , Hildesheim A 14 , International Nasopharyngeal Carcinoma (NPC) Genetics Working Group

Affiliations 

  • 1 Department of Experimental Research, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
  • 2 Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine and Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
  • 3 Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
  • 4 Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
  • 5 Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
  • 6 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University and Genomics Research Center, Academia Sinica, Taipei, Taiwan
  • 7 Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France
  • 8 Chang Gung Molecular Medicine Research Center and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
  • 9 Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia
  • 10 Department of Otorhinolaryngology, Hospital Pulau Pinang, Penang, Malaysia
  • 11 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia
  • 12 Beijing Proteome Research Center, Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine
  • 13 Genome Institute of Singapore, Singapore
  • 14 Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Cancer Epidemiol Biomarkers Prev, 2016 Jan;25(1):188-192.
PMID: 26545403 DOI: 10.1158/1055-9965.EPI-15-0144

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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