title: Genome-wide haplotype association analysis identifies SERPINB9, SERPINE2, GAK, and HSP90B1 as novel risk genes for oral squamous cell carcinoma.
abstract: The oral squamous cell carcinoma (OSCC) is one of the most common malignant epithelial neoplasms and considered to be caused by the genetic damage. In addition, smoking habit and excessive alcohol consumption have been estimated to be the main risk factors. Although the association between OSCC and genetic susceptibility loci has been observed in many different populations, most of these studies simply focused on the single nucleotide polymorphism. Therefore, we made a contrast analysis between the 112 OSCC patients from the GEO database and 245 normal samples from the HapMap project. First, we performed a genome-wide haplotype association study by comparing the frequency of the haplotypes in the case-control experiment. Then, we mapped the haplotypes to the corresponding genes, screened the risk genes according to significant haplotypes (P < 1E-04), and prioritized the OSCC genes based on their similarity to the known OSCC susceptibility genes. We filtered four OSCC genes including SERPINB9, SERPINE2, GAK, and HSP90B1 through the gene global prioritization score (P < 0.005). SERPINB9 ranked first in the candidate gene list and contained a significant haplotype TAGGA (P value = 3.12E-11). The second risk gene was SERPINE2 with the haplotype GGGCCCTTT, which was closely similar to the SERPINB9.
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
authors: Wei
authors: W
authors: Sun
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
authors: Wenhua
authors: W
authors: Lv
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
authors: Hongchao
authors: H
authors: Lv
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. zhangruijie2013@gmail.com.
authors: Ruijie
authors: R
authors: Zhang
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. jiangyongshuai@gmail.com.
authors: Yongshuai
authors: Y
authors: Jiang
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D058258:Serpin E2 / Q000235:genetics*; D015843:Serpins / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C102316:SERPINB9 protein, human; C545486:SERPINE2 protein, human; D058258:Serpin E2; D015843:Serpins; C053387:endoplasmin; C486325:GAK protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Association study; Haplotype; OSCC; Risk gene