BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer

A PACGENE study

David B. Zhen, Kari G. Rabe, Steven Gallinger, Sapna Syngal, Ann G. Schwartz, Michael S Goggins, Ralph H Hruban, Michele L. Cote, Robert R. McWilliams, Nicholas Roberts, Lisa A. Cannon-Albright, Donghui Li, Kelsey Moyes, Richard J. Wenstrup, Anne Renee Hartman, Daniela Seminara, Alison Klein, Gloria M. Petersen

Research output: Contribution to journalArticle

Abstract

Purpose:Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.Methods:Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.Results:Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.Conclusion:Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med 17 7, 569-577.

Original languageEnglish (US)
Pages (from-to)569-577
Number of pages9
JournalGenetics in Medicine
Volume17
Issue number7
DOIs
StatePublished - Jul 2 2015

Fingerprint

Pancreatic Neoplasms
Mutation
Genetic Testing
Genes
Viverridae
Germ Cells
Ovarian Neoplasms
Melanoma
Odds Ratio
Confidence Intervals
Breast Neoplasms
DNA

Keywords

  • BRCA1
  • BRCA2
  • CDKN2A
  • familial pancreatic cancer
  • PALB2

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Zhen, D. B., Rabe, K. G., Gallinger, S., Syngal, S., Schwartz, A. G., Goggins, M. S., ... Petersen, G. M. (2015). BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: A PACGENE study. Genetics in Medicine, 17(7), 569-577. https://doi.org/10.1038/gim.2014.153

BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer : A PACGENE study. / Zhen, David B.; Rabe, Kari G.; Gallinger, Steven; Syngal, Sapna; Schwartz, Ann G.; Goggins, Michael S; Hruban, Ralph H; Cote, Michele L.; McWilliams, Robert R.; Roberts, Nicholas; Cannon-Albright, Lisa A.; Li, Donghui; Moyes, Kelsey; Wenstrup, Richard J.; Hartman, Anne Renee; Seminara, Daniela; Klein, Alison; Petersen, Gloria M.

In: Genetics in Medicine, Vol. 17, No. 7, 02.07.2015, p. 569-577.

Research output: Contribution to journalArticle

Zhen, DB, Rabe, KG, Gallinger, S, Syngal, S, Schwartz, AG, Goggins, MS, Hruban, RH, Cote, ML, McWilliams, RR, Roberts, N, Cannon-Albright, LA, Li, D, Moyes, K, Wenstrup, RJ, Hartman, AR, Seminara, D, Klein, A & Petersen, GM 2015, 'BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: A PACGENE study', Genetics in Medicine, vol. 17, no. 7, pp. 569-577. https://doi.org/10.1038/gim.2014.153
Zhen, David B. ; Rabe, Kari G. ; Gallinger, Steven ; Syngal, Sapna ; Schwartz, Ann G. ; Goggins, Michael S ; Hruban, Ralph H ; Cote, Michele L. ; McWilliams, Robert R. ; Roberts, Nicholas ; Cannon-Albright, Lisa A. ; Li, Donghui ; Moyes, Kelsey ; Wenstrup, Richard J. ; Hartman, Anne Renee ; Seminara, Daniela ; Klein, Alison ; Petersen, Gloria M. / BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer : A PACGENE study. In: Genetics in Medicine. 2015 ; Vol. 17, No. 7. pp. 569-577.
@article{656468c722c34e4cbad3401bc66b9810,
title = "BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: A PACGENE study",
abstract = "Purpose:Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.Methods:Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.Results:Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2{\%}; BRCA2, 3.7{\%}; PALB2, 0.6{\%}; and CDKN2A, 2.5{\%}. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0{\%}) than nonfamilial pancreatic cancer probands (3.5{\%}) (odds ratio: 2.40; 95{\%} confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4{\%}, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.Conclusion:Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med 17 7, 569-577.",
keywords = "BRCA1, BRCA2, CDKN2A, familial pancreatic cancer, PALB2",
author = "Zhen, {David B.} and Rabe, {Kari G.} and Steven Gallinger and Sapna Syngal and Schwartz, {Ann G.} and Goggins, {Michael S} and Hruban, {Ralph H} and Cote, {Michele L.} and McWilliams, {Robert R.} and Nicholas Roberts and Cannon-Albright, {Lisa A.} and Donghui Li and Kelsey Moyes and Wenstrup, {Richard J.} and Hartman, {Anne Renee} and Daniela Seminara and Alison Klein and Petersen, {Gloria M.}",
year = "2015",
month = "7",
day = "2",
doi = "10.1038/gim.2014.153",
language = "English (US)",
volume = "17",
pages = "569--577",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer

T2 - A PACGENE study

AU - Zhen, David B.

AU - Rabe, Kari G.

AU - Gallinger, Steven

AU - Syngal, Sapna

AU - Schwartz, Ann G.

AU - Goggins, Michael S

AU - Hruban, Ralph H

AU - Cote, Michele L.

AU - McWilliams, Robert R.

AU - Roberts, Nicholas

AU - Cannon-Albright, Lisa A.

AU - Li, Donghui

AU - Moyes, Kelsey

AU - Wenstrup, Richard J.

AU - Hartman, Anne Renee

AU - Seminara, Daniela

AU - Klein, Alison

AU - Petersen, Gloria M.

PY - 2015/7/2

Y1 - 2015/7/2

N2 - Purpose:Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.Methods:Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.Results:Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.Conclusion:Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med 17 7, 569-577.

AB - Purpose:Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.Methods:Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.Results:Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.Conclusion:Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med 17 7, 569-577.

KW - BRCA1

KW - BRCA2

KW - CDKN2A

KW - familial pancreatic cancer

KW - PALB2

UR - http://www.scopus.com/inward/record.url?scp=84942550897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942550897&partnerID=8YFLogxK

U2 - 10.1038/gim.2014.153

DO - 10.1038/gim.2014.153

M3 - Article

VL - 17

SP - 569

EP - 577

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 7

ER -