title: Contribution of environment and genetics to pancreatic cancer susceptibility.
abstract: Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00 ± 0.05) versus both healthy unrelated and related controls (0.70 ± 0.06, p<0.001 and 0.82 ± 0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA -308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.
authors.affiliation: Department of Environmental Health, Indiana University, Bloomington, Indiana, United States of America; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hocevar
authors.affiliation: Department of Environmental Health, Indiana University, Bloomington, Indiana, United States of America; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kamendulis
authors.affiliation: Department of Environmental Health, Indiana University, Bloomington, Indiana, United States of America.
authors.forename: Xinzhu
authors.initials: X
authors.lastname: Pu
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Perkins
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Zheng-Yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Johnston
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: DeWitt
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loehrer
authors.affiliation: Department of Environmental Health, Indiana University, Bloomington, Indiana, United States of America; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Klaunig
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America; University of Washington, Seattle, Washington, United States of America.
authors.forename: E Gabriela
authors.initials: EG
authors.lastname: Chiorean
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D004249:DNA Damage; D003710:Demography; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor