Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer
Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved..
BACKGROUND & AIMS: We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer.
METHODS: The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve the precision of BRCA2 prevalence estimates, 290 probands were selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort.
RESULTS: Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%-5.6%). Carrier status was associated significantly with breast cancer in the proband or first-degree relative (P < .01), and with colorectal cancer in the proband or first-degree relative (P < .01), but not family history of pancreatic cancer, age at diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (95% confidence interval, 4.4%-17.0%) and 11.1% (95% confidence interval, 3.0%-19.1%) carried pathogenic mutations, respectively.
CONCLUSIONS: A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
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| Enthalten in: |
Gastroenterology - 148(2015), 3 vom: 01. März, Seite 556-64 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Grant, Robert C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.04.2015 Date Revised 22.03.2024 published: Print-Electronic CommentOn: Gastroenterology. 2015 Mar;148(3):459-61 Citation Status MEDLINE |
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| doi: |
10.1053/j.gastro.2014.11.042 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer |
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| 500 | |a CommentOn: Gastroenterology. 2015 Mar;148(3):459-61 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND & AIMS: We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer | ||
| 520 | |a METHODS: The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve the precision of BRCA2 prevalence estimates, 290 probands were selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort | ||
| 520 | |a RESULTS: Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%-5.6%). Carrier status was associated significantly with breast cancer in the proband or first-degree relative (P < .01), and with colorectal cancer in the proband or first-degree relative (P < .01), but not family history of pancreatic cancer, age at diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (95% confidence interval, 4.4%-17.0%) and 11.1% (95% confidence interval, 3.0%-19.1%) carried pathogenic mutations, respectively | ||
| 520 | |a CONCLUSIONS: A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Comment | |
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| 700 | 1 | |a Holter, Spring |e verfasserin |4 aut | |
| 700 | 1 | |a Gallinger, Steven |e verfasserin |4 aut | |
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