title: A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.
abstract: BACKGROUND
  Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.
  
  
  METHODS
  A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).
  
  
  RESULTS
  Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.
  
  
  CONCLUSIONS
  Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.|Translational Genomics Lab, High Impact Research Building (Level 2), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Joyce Siew Yong
authors.initials: JS
authors.lastname: Low
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.|Translational Genomics Lab, High Impact Research Building (Level 2), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yoon Ming
authors.initials: YM
authors.lastname: Chin
authors.affiliation: Laboratory for Pharmacogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.affiliation: Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Gopala Krishnan
authors.initials: GK
authors.lastname: Govindasamy
authors.affiliation: Department of Otorhinolaryngology, Hospital Pulau Pinang, Penang, Malaysia.
authors.forename: Kin Choo
authors.initials: KC
authors.lastname: Pua
authors.affiliation: Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Yoke Yeow
authors.initials: YY
authors.lastname: Yap
authors.affiliation: Department of Oral Biology & Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Sarawak General Hospital, Sarawak, Malaysia.
authors.forename: Selva Kumar
authors.initials: SK
authors.lastname: Subramaniam
authors.affiliation: ENT Department, Hospital Queen Elizabeth, Karung Berkunci No. 2029, Kota Kinabalu, Sabah, Malaysia.
authors.forename: Cheng Ai
authors.initials: CA
authors.lastname: Ong
authors.affiliation: Department of Otorhinolaryngology, Sarawak General Hospital, Kuching, Sarawak, Malaysia.
authors.forename: Tee Yong
authors.initials: TY
authors.lastname: Tan
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: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.|Translational Genomics Lab, High Impact Research Building (Level 2), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ching Ching
authors.initials: CC
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002277:Carcinoma; D002681:China / Q000208:ethnology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult