Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk

Robert R Mc Williams, William R. Bamlet, Mariza De Andrade, David N. Rider, Fergus J Couch, Julie M Cunningham, Martha E. Matsumoto, Kari G. Rabe, Traci J. Hammer, Gloria M Petersen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Inherited risk of pancreatic cancer has been associated with mutations in several genes, including BRCA2, CDKN2A (p16), PRSS1, and PALB2. We hypothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development. Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-eight genes directly and indirectly involved in the Fanconi/BRCA pathway (includes BRCA1, BRCA2, and PALB2) were identified and 248 tag SNPs were selected. In addition, 11 SNPs in CDKN2A, PRSS1, and PRSS2 were selected. Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was used to investigate pathway effects. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed. Results: Gene level analyses showed no significant association of any genes with altered pancreatic cancer risk. Multiple single SNP analyses showed associations, which will require replication. Exploratory pathway analyses by recursive partitioning showed no association between SNPs and risk for pancreatic cancer. Conclusion: In a candidate gene and pathway SNP association study analysis, common variations in the Fanconi/BRCA pathway and other candidate familial pancreatic cancer genes are not associated with risk for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)2549-2552
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number9
DOIs
StatePublished - Sep 2009

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Neoplasm Genes
Pancreatic Neoplasms
Single Nucleotide Polymorphism
Genes
BRCA2 Gene
Gene-Environment Interaction
Principal Component Analysis
Case-Control Studies
Adenocarcinoma
Mutation

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk. / Mc Williams, Robert R; Bamlet, William R.; De Andrade, Mariza; Rider, David N.; Couch, Fergus J; Cunningham, Julie M; Matsumoto, Martha E.; Rabe, Kari G.; Hammer, Traci J.; Petersen, Gloria M.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 18, No. 9, 09.2009, p. 2549-2552.

Research output: Contribution to journalArticle

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abstract = "Background: Inherited risk of pancreatic cancer has been associated with mutations in several genes, including BRCA2, CDKN2A (p16), PRSS1, and PALB2. We hypothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development. Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-eight genes directly and indirectly involved in the Fanconi/BRCA pathway (includes BRCA1, BRCA2, and PALB2) were identified and 248 tag SNPs were selected. In addition, 11 SNPs in CDKN2A, PRSS1, and PRSS2 were selected. Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was used to investigate pathway effects. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed. Results: Gene level analyses showed no significant association of any genes with altered pancreatic cancer risk. Multiple single SNP analyses showed associations, which will require replication. Exploratory pathway analyses by recursive partitioning showed no association between SNPs and risk for pancreatic cancer. Conclusion: In a candidate gene and pathway SNP association study analysis, common variations in the Fanconi/BRCA pathway and other candidate familial pancreatic cancer genes are not associated with risk for pancreatic cancer.",
author = "{Mc Williams}, {Robert R} and Bamlet, {William R.} and {De Andrade}, Mariza and Rider, {David N.} and Couch, {Fergus J} and Cunningham, {Julie M} and Matsumoto, {Martha E.} and Rabe, {Kari G.} and Hammer, {Traci J.} and Petersen, {Gloria M}",
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T1 - Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk

AU - Mc Williams, Robert R

AU - Bamlet, William R.

AU - De Andrade, Mariza

AU - Rider, David N.

AU - Couch, Fergus J

AU - Cunningham, Julie M

AU - Matsumoto, Martha E.

AU - Rabe, Kari G.

AU - Hammer, Traci J.

AU - Petersen, Gloria M

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N2 - Background: Inherited risk of pancreatic cancer has been associated with mutations in several genes, including BRCA2, CDKN2A (p16), PRSS1, and PALB2. We hypothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development. Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-eight genes directly and indirectly involved in the Fanconi/BRCA pathway (includes BRCA1, BRCA2, and PALB2) were identified and 248 tag SNPs were selected. In addition, 11 SNPs in CDKN2A, PRSS1, and PRSS2 were selected. Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was used to investigate pathway effects. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed. Results: Gene level analyses showed no significant association of any genes with altered pancreatic cancer risk. Multiple single SNP analyses showed associations, which will require replication. Exploratory pathway analyses by recursive partitioning showed no association between SNPs and risk for pancreatic cancer. Conclusion: In a candidate gene and pathway SNP association study analysis, common variations in the Fanconi/BRCA pathway and other candidate familial pancreatic cancer genes are not associated with risk for pancreatic cancer.

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