title: How genome-wide SNP-SNP interactions relate to nasopharyngeal carcinoma susceptibility.
abstract: This study is the first to use genome-wide association study (GWAS) data to evaluate the multidimensional genetic architecture underlying nasopharyngeal cancer. Since analysis of data from GWAS confirms a close and consistent association between elevated risk for nasopharyngeal carcinoma (NPC) and major histocompatibility complex class 1 genes, our goal here was to explore lesser effects of gene-gene interactions. We conducted an exhaustive genome-wide analysis of GWAS data of NPC, revealing two-locus interactions occurring between single nucleotide polymorphisms (SNPs), and identified a number of suggestive interaction loci which were missed by traditional GWAS analyses. Although none of the interaction pairs we identified passed the genome-wide Bonferroni-adjusted threshold for significance, using independent GWAS data from the same population (Stage 2), we selected 66 SNP pairs in 39 clusters with P<0.01. We identified that in several chromosome regions, multiple suggestive interactions group to form a block-like signal, effectively reducing the rate of false discovery. The strongest cluster of interactions involved the CREB5 gene and a SNP rs1607979 on chromosome 17q22 (P = 9.86×10(-11)) which also show trans-expression quantitative loci (eQTL) association in Chinese population. We then detected a complicated cis-interaction pattern around the NPC-associated HLA-B locus, which is immediately adjacent to copy-number variations implicated in male susceptibility for NPC. While it remains to be seen exactly how and to what degree SNP-SNP interactions such as these affect susceptibility for nasopharyngeal cancer, future research on these questions holds great promise for increasing our understanding of this disease's genetic etiology, and possibly also that of other gene-related cancers.
authors.affiliation: Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan ; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan ; Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Su
authors.affiliation: Genomic Research Branch, Division of Neuroscience and Behavioral Sciences, National Institute of Mental Health, NIH, Bethesda, Maryland, United States of America ; Department of Gastroenterology, Johns Hopkins Medical School, Baltimore, Maryland, United States of America.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yao Shugart
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan.
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tsang
authors.affiliation: Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ka-Po
authors.initials: KP
authors.lastname: Tse
authors.affiliation: Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
mesh_terms: D002277:Carcinoma; D016000:Cluster Analysis; D051699:Cyclic AMP Response Element-Binding Protein A / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015235:HLA-B Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: C497102:CREB5 protein, human; D051699:Cyclic AMP Response Element-Binding Protein A; D015235:HLA-B Antigens