Genome-wide haplotype association analysis identifies SERPINB9, SERPINE2, GAK, and HSP90B1 as novel risk genes for oral squamous cell carcinoma

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.