Exome-Wide Association Study of Pancreatic Cancer Risk
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:154 |
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| Enthalten in: |
Gastroenterology - 154(2018), 3 vom: 26. Feb., Seite 719-722.e3 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Grant, Robert C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.05.2018 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1053/j.gastro.2017.10.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM277423368 |
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| 520 | |a Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Familial Cancer | |
| 650 | 4 | |a Inherited Cancer | |
| 650 | 4 | |a Pancreas | |
| 650 | 4 | |a Rare Variant Burden Tests | |
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| 700 | 1 | |a Denroche, Robert E |e verfasserin |4 aut | |
| 700 | 1 | |a Borgida, Ayelet |e verfasserin |4 aut | |
| 700 | 1 | |a Virtanen, Carl |e verfasserin |4 aut | |
| 700 | 1 | |a Cook, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Alyssa L |e verfasserin |4 aut | |
| 700 | 1 | |a Connor, Ashton A |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Julie M |e verfasserin |4 aut | |
| 700 | 1 | |a Peterson, Gloria |e verfasserin |4 aut | |
| 700 | 1 | |a Roberts, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Klein, Alison P |e verfasserin |4 aut | |
| 700 | 1 | |a Grimmond, Sean M |e verfasserin |4 aut | |
| 700 | 1 | |a Biankin, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Cleary, Sean |e verfasserin |4 aut | |
| 700 | 1 | |a Moore, Malcolm |e verfasserin |4 aut | |
| 700 | 1 | |a Lemire, Mathieu |e verfasserin |4 aut | |
| 700 | 1 | |a Zogopoulos, George |e verfasserin |4 aut | |
| 700 | 1 | |a Stein, Lincoln |e verfasserin |4 aut | |
| 700 | 1 | |a Gallinger, Steven |e verfasserin |4 aut | |
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