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.

据估计，与非犹太人相比，犹太人患胰腺癌的风险更高，但他们观察到的 50-80% 的额外风险并不能用已知的非遗传或遗传风险因素来解释。我们在 dbGaP、PanScan I/II、PanC4 和 GERA 数据集中确定的美国犹太人（主要是德系犹太人）的病例对照样本中进行了 GWAS，其中包括 406 名胰腺癌患者和 2332 名对照。然后我们检查了P  < 10 ^–7的 SNP在扩展的样本集中，来自相同数据集的 539 名完全或部分犹太人胰腺癌患者和 4117 名完全或部分犹太人对照。犹太血统是使用种子 FastPCA 基因确定的。在全部犹太人中，在染色体 19p12 ​​上检测到一种新的全基因组显着关联（rs66562280，每个等位基因 OR = 1.55，95% CI = 1.33–1.81，P  = ^10–7.6）。在染色体 19p13.3 上检测到暗示性的相对独立关联（rs2656937，OR = 1.53，95% CI = 1.31–1.78，P  = ^10–7.0）。在全部和部分犹太人的组合中，这些 SNP 也出现了类似的关联。这是第一次在高危犹太人群中针对胰腺癌进行 GWAS。SNP rs66562280 和 rs2656937 分别位于ZNF100-like和ARRDC5的内含子中，并且已知会改变在胰腺癌发生中发挥不可或缺作用的基因的调控基序。