Open AccessA pooled genome-wide association study identifies pancreatic cancer susceptibility loci on chromosome 19p12 and 19p13.3 in the full-Jewish population
Author(s) -
Samantha A. Streicher,
Alison P. Klein,
Sara H. Olson,
Robert C. Kurtz,
Laufey T. Ámundadóttir,
Andrew T. DeWan,
Hongyu Zhao,
Harvey A. Risch
Publication year - 2020
Publication title -
human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.351
H-Index - 137
eISSN - 1432-1203
pISSN - 0340-6717
DOI - 10.1007/s00439-020-02205-8
Subject(s) - genome wide association study , single nucleotide polymorphism , biology , genetics , pancreatic cancer , genetic association , population , allele , 1000 genomes project , case control study , cancer , allele frequency , oncology , gene , medicine , genotype , environmental health
Jews 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 examined resulting SNPs with P < 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 of ZNF100-like and ARRDC5, respectively, and are known to alter regulatory motifs of genes that play integral roles in pancreatic carcinogenesis.