Journal Article

Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility

Klaunig, James E., Hocevar, Barbara A., Wang, Zheng-Yu, Loehrer, Patrick J., Kamendulis, Lisa M., Pu, Xinzhu, Li, Lang, Johnston, Erica L., Perkins, Susan M., DeWitt, John M., Chiorean, E. Gabriela

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Aged, 80 and over / Antioxidants / Antioxidants (Nutrients) / Bioassays / Biology and Life Sciences / Biomarkers / Biomarkers, Tumor - metabolism / Breast cancer / Cancer / Cancer genetics / Cancer research / Case-Control Studies / Cell cycle / Comet assay / Damage assessment / Damage detection / Defense mechanisms / Demography / Deoxyribonucleic acid / Diabetes / Diabetes mellitus / Disease prevention / Disease susceptibility / DNA / DNA Damage / DNA repair / Environment / Environmental factors / Environmental health / Female / Genes / Genetic polymorphisms / Genetic Predisposition to Disease / Genetics / Health risk assessment / Health risks / Humans / Lifestyles / Lipids / Male / Malondialdehyde / Medical prognosis / Medicine / Medicine and Health Sciences / Metabolism / Middle Aged / Oxidative Stress / Pancreatic cancer / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - pathology / Pancreatitis / Polymorphism, Single Nucleotide - genetics / Radiation therapy / Risk analysis / Risk factors / Rodents / Single-nucleotide polymorphism / Smoking / Standard error / Studies / TNF inhibitors / Toxicity / Tumor necrosis factor-α / Type 2 diabetes / Young Adult