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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

Low JS 1 , Chin YM 1 , Mushiroda T 2 , Kubo M 3 , Govindasamy GK 4 , Pua KC 5 Show all authors , Yap YY 6 , Yap LF 7 , Subramaniam SK 8 , Ong CA 9 , Tan TY 10 , Khoo AS 11 , Malaysian NPC Study Group , Ng CC 1

Affiliations 

  • 1 Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
  • 2 Laboratory for Pharmacogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 3 Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 4 Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 5 Department of Otorhinolaryngology, Hospital Pulau Pinang, Penang, Malaysia
  • 6 Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Kuala Lumpur, Malaysia
  • 7 Department of Oral Biology & Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
  • 8 Department of Otorhinolaryngology, Head and Neck Surgery, Sarawak General Hospital, Sarawak, Malaysia
  • 9 ENT Department, Hospital Queen Elizabeth, Karung Berkunci No. 2029, Kota Kinabalu, Sabah, Malaysia
  • 10 Department of Otorhinolaryngology, Sarawak General Hospital, Kuching, Sarawak, Malaysia
  • 11 Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia
PLoS One, 2016;11(1):e0145774.
PMID: 26730743 DOI: 10.1371/journal.pone.0145774

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.

CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

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

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