title: A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry.
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.
  
  
  CONCLUSIONS
  Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis.
authors.affiliation: 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.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.affiliation: Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine and Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Su
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ching-Ching
authors.initials: CC
authors.lastname: Ng
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yoon-Ming
authors.initials: YM
authors.lastname: Chin
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
authors.affiliation: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University and Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Wan-Lun
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.affiliation: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University and Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Chang Gung Molecular Medicine Research Center and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Fu-Tuo
authors.initials: FT
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Qi-Shen
authors.initials: QS
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Yun-Miao
authors.initials: YM
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.affiliation: Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Alan Soo-Beng
authors.initials: AS
authors.lastname: Khoo
authors.affiliation: 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.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Mo
authors.affiliation: Department of Otorhinolaryngology, Hospital Pulau Pinang, Penang, Malaysia.
authors.forename: Kin-Choo
authors.initials: KC
authors.lastname: Pua
authors.affiliation: Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Soo-Hwang
authors.initials: SH
authors.lastname: Teo
authors.affiliation: Chang Gung Molecular Medicine Research Center and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ka-Po
authors.initials: KP
authors.lastname: Tse
authors.affiliation: 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.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Xia
authors.affiliation: Beijing Proteome Research Center, Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Proteome Research Center, Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine.
authors.forename: Gang-Qiao
authors.initials: GQ
authors.lastname: Zhou
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: 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.|Peking Union Medical College, Beijing, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D044466:Asian People; D002277:Carcinoma; D016022:Case-Control Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D019098:Telomerase / Q000235:genetics*
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase