Novel genetic locus at MHC region for esophageal squamous cell carcinoma in Chinese populations

Background Our previous genome-wide association study (GWAS) identified three independent single nucleotide polymorphisms (SNPs) in human major histocompatibility complex (MHC) region showing association with esophageal squamous cell carcinoma (ESCC). In this study, we increased GWAS sample size on MHC region and performed validation in an independent ESCC cases and normal controls with aim to find additional loci at MHC region showing association with an increased risk to ESCC. Methods The 1,077 ESCC cases and 1,733 controls were genotyped using Illumina Human 610-Quad Bead Chip, and 451 cases and 374 controls were genotyped using Illumina Human 660W-Quad Bead Chip. After quality control, the selected SNPs were replicated by TaqMan genotyping assay on another 2,026 ESCC cases and 2,384 normal controls. Results By excluding low quality SNPs in primary GWAS screening, we selected 2,533 SNPs in MHC region for association analysis, and identified 5 SNPs with p < 10(-4). Further validation analysis in an independent case-control cohort confirmed one of the 5 SNPs (rs911178) that showed significant association with ESCC. rs911178 (P-GWAS = 6.125E-04, OR = 0.644 and P-replication = 1.406E-22, OR = 0.489) was located at upstream of SCAND3. Conclusion The rs911178 (SCAND3 gene) in MHC region is significantly associated with high risk of ESCC. This study not only reveal the potential role of MHC region for the pathogenesis of ESCC, but also provides important clues for the establishment of tools and methods for screening high risk population of ESCC.