A pooled genome-wide association study identifies pancreatic cancer susceptibility loci on chromosome 19p12 and 19p13.3 in the full-Jewish population Journal Article
| Authors: | Streicher, S. A.; Klein, A. P.; Olson, S. H.; Kurtz, R. C.; Amundadottir, L. T.; DeWan, A. T.; Zhao, H.; Risch, H. A. |
| Article Title: | A pooled genome-wide association study identifies pancreatic cancer susceptibility loci on chromosome 19p12 and 19p13.3 in the full-Jewish population |
| Abstract: | 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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. |
| Journal Title: | Human Genetics |
| Volume: | 140 |
| Issue: | 2 |
| ISSN: | 0340-6717 |
| Publisher: | Springer |
| Date Published: | 2021-02-01 |
| Start Page: | 309 |
| End Page: | 319 |
| Language: | English |
| DOI: | 10.1007/s00439-020-02205-8 |
| PUBMED: | 32671597 |
| PROVIDER: | scopus |
| PMCID: | PMC8395137 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work