title: A gender-specific association of CNV at 6p21.3 with NPC susceptibility.
abstract: Copy number variations (CNVs), a major source of human genetic polymorphism, have been suggested to have an important role in genetic susceptibility to common diseases such as cancer, immune diseases and neurological disorders. Nasopharyngeal carcinoma (NPC) is a multifactorial tumor closely associated with genetic background and with a male preponderance over female (3:1). Previous genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that are associated with NPC susceptibility. Here, we sought to explore the possible association of CNVs with NPC predisposition. Utilizing genome-wide SNP-based arrays and five CNV-prediction algorithms, we identified eight regions with CNV that were significantly overrepresented in NPC patients compared with healthy controls. These CNVs included six deletions (on chromosomes 3, 6, 7, 8 and 19), and two duplications (on chromosomes 7 and 12). Among them, the CNV located at chromosome 6p21.3, with single-copy deletion of the MICA and HCP5 genes, showed the highest association with NPC. Interestingly, it was more specifically associated with an increased NPC risk among males. This gender-specific association was replicated in an independent case-control sample using a self-established deletion-specific polymerase chain reaction strategy. To the best of our knowledge, this is the first study to explore the role of constitutional CNVs in NPC, using a genome-wide platform. Moreover, we identified eight novel candidate regions with CNV that merit future investigation, and our results suggest that similar to neuroblastoma and prostate cancer, genetic structural variations might contribute to NPC predisposition.
authors.affiliation: Genome Medicine Core, Chang Gung Molecular Medicine Research Center, Graduate Institute of Biomedical Sciences, Chang Gung University, No. 259 Wen-Hwa 1st Road, Kwei-shan,Taoyuan 333, Taiwan.
authors.forename: Ka-Po
authors.initials: KP
authors.lastname: Tse
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Su
authors.forename: Min-lee
authors.initials: ML
authors.lastname: Yang
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Cheng
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tsang
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Sheng-Po
authors.initials: SP
authors.lastname: Hao
authors.forename: Yin
authors.initials: Y
authors.lastname: Yao Shugart
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002277:Carcinoma; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D055106:Genome-Wide Association Study; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012307:Risk Factors; D012727:Sex Characteristics; D012737:Sex Factors
chemical_list: C080521:HCP5 long noncoding RNA, human; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated