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


CONCLUSIONS
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.
McWilliams
Robert R
RR
Department of Oncology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA. Mcwilliams.robert@mayo.edu
Bamlet
William R
WR
de Andrade
Mariza
M
Rider
David N
DN
Couch
Fergus J
FJ
Cunningham
Julie M
JM
Matsumoto
Martha E
ME
Rabe
Kari G
KG
Hammer
Traci J
TJ
Petersen
Gloria M
GM
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
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