Grant, R. C. et al. (2018) Exome-wide association study of pancreatic cancer risk. Gastroenterology, 154(3), 719-722.e3. (doi: 10.1053/j.gastro.2017.10.015) (PMID:29074453) (PMCID:PMC5811358)
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Abstract
We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition.
| Item Type: | Articles |
|---|---|
| Keywords: | Familial cancer, inherited cancer, pancreas, rare variant burden tests. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Biankin, Professor Andrew and Grimmond, Professor Sean |
| Authors: | Grant, R. C., Denroche, R. E., Borgida, A., Virtanen, C., Cook, N., Smith, A. L., Connor, A. A., Wilson, J. M., Peterson, G., Roberts, N. J., Klein, A. P., Grimmond, S. M., Biankin, A., Cleary, S., Moore, M., Lemire, M., Zogopolous, G., Stein, L., and Gallinger, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Gastroenterology |
| Publisher: | Elsevier |
| ISSN: | 0016-5085 |
| ISSN (Online): | 1528-0012 |
| Published Online: | 23 October 2017 |
| Copyright Holders: | Copyright © 2017 The AGA Institute |
| First Published: | First published in Gastroenterology 154(3): 719-722.e3 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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