Contribution of environment and genetics to oxidative stress in pancreatic cancer (PC) patients (pts).

Abstract

211 Background: Several risk factors have been identified as contributors to PC development, including tobacco and alcohol use, and exposure to environmental chemicals. A common denominator of these risk factors is the ability to induce oxidative stress/damage. An individual's genetic makeup may also contribute to oxidative stress, as oxidative stress/damage genes exhibit single nucleotide polymorphisms (SNPs), which can alter protein expression or activity. The goal of this study was to (1) determine if increased oxidative stress/damage is observed in PC pts and (2) to assess the contribution of environmental and genetic factors to oxidative stress/damage parameters. Methods: An oxidative stress/damage profile was generated from blood samples of newly diagnosed PC pts (n=20), from non-cohabiting genetic relatives (n=20) and/or from non-genetic relatives living in the same household (n=20). This profile consisted of measurement of total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), direct and oxidative DNA damage (COMET), and malondialdehyde (MDA) levels. Expression of SNPs in selected oxidative stress/response genes was also evaluated. Environmental and dietary/lifestyle information was collected using a detailed questionnaire. Results: PC pts, when compared to healthy nonrelated but cohabitating relatives, displayed a significant increase in direct DNA damage (p=0.002), while oxidative DNA damage, TEAC and MDA levels were similar. When comparing PC pts to healthy genetic relatives, increased levels of TEAC, direct and oxidative DNA damage approached or were statistically significant (p = 0.061, 0.002, and 0.062 respectively). Analysis of 26 selected SNPs in oxidative stress/ damage genes in the PC pts vs healthy controls revealed that expression of CYP2A6 (L160H), rs1801272, and TNF (-308G>A), rs1800629, approached statistical significance (p=0.05 and 0.20 respectively). Conclusions: Increased oxidative DNA damage observed in PC pts vs healthy related, but non-cohabitating relatives, suggests that environmental exposures contribute to oxidative stress. In combination with a specific genetic background, environmental influences may increase the risk of PC. No significant financial relationships to disclose.