title: Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.
abstract: Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10(-5)) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Childs
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Kari G
authors.initials: KG
authors.lastname: Chaffee
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Sapna
authors.initials: S
authors.lastname: Syngal
authors.affiliation: Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan.
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.affiliation: Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Cote
authors.affiliation: Baylor College of Medicine, Dan L. Duncan Cancer Center, Houston, Texas.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: David N
authors.initials: DN
authors.lastname: Rider
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Laufey T
authors.initials: LT
authors.lastname: Amundadottir
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Wolpin
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Goggins
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. aklein1@jhmi.edu.
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D053843:DNA Mismatch Repair; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D009687:Nuclear Proteins