A pooled genome-wide association study identifies pancreatic cancer susceptibility loci on chromosome 19p12 and 19p13.3 in the full-Jewish population

AbstractJews are estimated to be at increased risk of pancreatic cancer compared to non-Jews, but their observed 50 –80% excess risk is not explained by known non-genetic or genetic risk factors. We conducted a GWAS in a case–control sample of American Jews, largely Ashkenazi, including 406 pancreatic cancer patients and 2332 controls, identified in the dbGaP, PanScan I/II, PanC4 and GERA data sets. We then e xamined resulting SNPs withP <  10–7 in an expanded sample set, of 539 full- or part-Jewish pancreatic cancer patients and 4117 full- or part-Jewish controls from the same data sets. Jewish ancestries were genetically determined using seeded FastPCA. Among the full Jews, a novel genome-wide significant association was detected on chromosome 19p12 (rs66562280, per-allele OR  = 1.55, 95% CI = 1.33–1.81,P = 10–7.6). A suggestive relatively independent association was detected on chromosome 19p13.3 (rs2656937, OR  = 1.53, 95% CI = 1.31–1.78,P = 10–7.0). Similar associations were seen for these SNPs among the full and part Jews combined. This is the first GWAS conducted for pancreatic cancer in the increased-risk Jewish population. The SNPs rs66562280 and rs2656937 are located in introns ofZNF100-like andARRDC5, respectively, and are known to alter regulatory motifs of genes that play integral roles in pancreatic carcinogenesis.

Source: Human Genetics - July 14, 2020 Category: Genetics & Stem Cells Source Type: research