Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

作者: Mingfeng Zhang , Zhaoming Wang , Ofure Obazee , Jinping Jia , Erica J Childs

DOI: 10.18632/ONCOTARGET.11041

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摘要: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new variants, we performed imputation based on 1000 Genomes (1000G) Project data and analysis using 5,107 case 8,845 control subjects from 27 cohort case-control that participated the PanScan I-III GWAS. This analysis, combination with a two-staged replication an additional 6,076 7,555 PANcreatic Disease ReseArch (PANDoRA) Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P 4.88x10 -15), rs10094872 8q24.21 (OR 1.15, 3.22x10 -9) rs35226131 5p15.33 0.71, 1.70x10 -8). These SNPs represent independent previously chr1q32.1 ( NR5A2), chr8q24.21 MYC) chr5p15.33 CLPTM1L- TERT) as per analyses conditioned reported variants. We assessed expression candidate genes three histologically normal n 10) tumor 8) derived tissue samples observed reduction NR5A2 (chr1q32.1) tumors (fold change -7.6, 5.7x10 finding was validated second set paired 20) (average fold for isoforms -31.3 to -95.7, 7.5x10 -4-2.0x10 -3). Our study has independently conferring merit functional follow-up target explain underlying biology.

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