Contribution of environment and genetics to pancreatic cancer susceptibility

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article numbere90052
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 20 2014

Fingerprint

pancreatic neoplasms
Pancreatic Neoplasms
DNA damage
DNA Damage
Oxidative stress
DNA
Oxidative Stress
oxidative stress
Control Groups
Comet Assay
pancreatitis
risk groups
smoking (food products)
Nutrition
Medical problems
Malondialdehyde
Polymorphism
drinking
Pancreatitis
malondialdehyde

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hocevar, B. A., Kamendulis, L. M., Pu, X., Perkins, S., Wang, Z. Y., Johnston, E. L., ... Chiorean, E. G. (2014). Contribution of environment and genetics to pancreatic cancer susceptibility. PLoS One, 9(3), [e90052]. https://doi.org/10.1371/journal.pone.0090052

Contribution of environment and genetics to pancreatic cancer susceptibility. / Hocevar, Barbara A.; Kamendulis, Lisa M.; Pu, Xinzhu; Perkins, Susan; Wang, Zheng Yu; Johnston, Erica L.; DeWitt, John; Li, Lang; Loehrer, Patrick; Klaunig, James E.; Chiorean, E. Gabriela.

In: PLoS One, Vol. 9, No. 3, e90052, 20.03.2014.

Research output: Contribution to journalArticle

Hocevar, BA, Kamendulis, LM, Pu, X, Perkins, S, Wang, ZY, Johnston, EL, DeWitt, J, Li, L, Loehrer, P, Klaunig, JE & Chiorean, EG 2014, 'Contribution of environment and genetics to pancreatic cancer susceptibility', PLoS One, vol. 9, no. 3, e90052. https://doi.org/10.1371/journal.pone.0090052
Hocevar, Barbara A. ; Kamendulis, Lisa M. ; Pu, Xinzhu ; Perkins, Susan ; Wang, Zheng Yu ; Johnston, Erica L. ; DeWitt, John ; Li, Lang ; Loehrer, Patrick ; Klaunig, James E. ; Chiorean, E. Gabriela. / Contribution of environment and genetics to pancreatic cancer susceptibility. In: PLoS One. 2014 ; Vol. 9, No. 3.
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