Abstract 4392: Oxidative damage to placental DNA, air pollution, genetic polymorphisms and pregnancy outcomes

Abstract

Abstract Oxidative stress to placenta DNA may result in negative pregnancy outcomes, including intrauterine growth retardation (IUGR) and low birth weight (LBW). The aim of our study was to investigate the association between the levels of 8-oxodeoxuanosine (8-oxodG), a marker of oxidative DNA damage, in placenta DNA, exposure to particulate matter <2.5 µm (PM2.5) and benzo[a]pyrene (B[a]P) during pregnancy, genetic polymorphisms in 97 genes and pregnancy outcomes in a group of 891 newborns born between the years 1994 and 1999 in the Czech Republic in two districts with different levels of air pollution. We observed a borderline difference in oxidative stress levels between the IUGR and non-IUGR group (median 8-oxodG/105 dG (range): 2.03 (0.29-6.17) and 1.74 (0.20-6.50), p=0.055, for the IUGR and non-IUGR group, respectively) and higher oxidative stress in the LBW newborns (median 8-oxodG/105 dG (range): 2.25 (0.27-6.25) and 1.75 (0.20-6.50), p<0.05, for the LBW and non-LBW group, respectively). Univariate regression analysis revealed single nucleotide polymorphisms (SNPs) in 12 genes (ADH1B, ALDH2, BCL6, CCL2, CTLA4, CXCL10, CYP1A2, CYP2D6, GATA3, IL13, MGMT, XPC) to be associated with 8-oxodG levels; IUGR was associated with SNPs in 6 genes (AHR, C5, CCL24, CTLA4, TLR4, XRCC3), while LBW with SNPs in 18 genes (ADH1C, CCL7, CCL8, CCL18, CYP1A1, ERCC3, HMOX1, IL10, LIG1, LTA, MBL2, STAT4, TOLLIP, TLR2, XPC, TP53, XRCC1, XRCC3). 8-oxodG levels were increased by exposure to PM2.5 in the first four moths of pregnancy; exposure to B[a]P had no effect. Multivariate-adjusted logistic regression revealed that newborns with above-median levels of 8-oxodG (>1.80 8-oxodG/105 dG) had 64% higher probability of IUGR (OR (95% CI): 1.64 (1.12-2.42), p<0.05) than newborns with below-median levels of oxidative DNA damage. Genetic polymorphisms in ADH1B, C5 and TLR4, as well as body mass index and the length of education of the mother also significantly affected the risk of IUGR. Oxidative DNA damage was not confirmed by multivariate-adjusted logistic regression to be a risk factor of LBW. Variables affecting LBW include genetic polymorphisms in CCL7, HMOX1 and STAT4, gender, mother's smoking and the length of gestation. In summary, our results suggest that oxidative DNA damage increases the risk of IUGR; exposure to air pollution during pregnancy is not a significant independent factor affecting 8-oxodG-related IUGR. Supported by the Czech Ministry of the Environment (SP/1b3/50/07). Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4392.