Abstract 2643: Interactions between polycyclic aromatic hydrocarbon exposure and genetic polymorphisms on benzo(a)pyrene-DNA adducts in a Polish cohort of mothers and newborns

Abstract

Abstract Background Polycyclic aromatic hydrocarbons (PAHs) are a class of chemicals common in the environment. Major sources of PAHs include fossil fuel combustion and cigarette smoking. Certain PAHs are carcinogenic, though the degree to which genetic variation influences susceptibility to PAH exposure remains unclear. Benzo(a)pyrene (BaP) is a well-studied PAH that is classified as a probable human carcinogen. Here, we evaluated single nucleotide polymorphism (SNP) frequency in genes related to PAH metabolism and detoxification, and explored the interactions between PAH exposure and SNPs on BaP-DNA adducts, an established cancer risk marker, in umbilical cord white blood cells (WBCs). Methods Maternal and umbilical cord blood were collected at delivery from participants in a longitudinal cohort study of Polish mothers and newborns in Krakow, Poland. WBC DNA was isolated from cord blood, and genetic polymorphisms and BaP-DNA cord adducts were then measured in 503 mothers and 445 newborns. Maternal PAH exposure was measured during pregnancy with a personal air exposure monitor. For this study 7 maternal and newborn genes related to PAH metabolism, detoxification and repair were selected for SNP analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. SNP x PAH interactions on logarithmic (ln)-transformed BaP-DNA adduct levels were explored. Results We observed a number of significant interactions between high PAH exposure and SNPs in both mothers and newborns on BaP-DNA adducts in cord blood. For example, the interaction between a CYP1A2 SNP (rs2069514) and high PAH exposure on cord BaP-DNA adducts in newborns was significant (α=−1.34, p<0.01). We will present significant interaction results from analyses performed on both maternal and newborn CYP1A1, CYP1A2, GSTM3, GSTT2, NQO1 and XRCC1 SNPs. Discussion It is biologically plausible that an individual's abilities to metabolically activate and detoxify BaP and repair DNA damage play a role in susceptibility to DNA adduct formation following prenatal PAH exposure. Ultimately, this susceptibility could correlate with future risk of cancer development. Our findings of several SNP x PAH exposure interactions on cord BaP-DNA adducts support the hypothesis that genetic variability can contribute to susceptibility and potential cancer risk from prenatal PAH exposures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2643. doi:1538-7445.AM2012-2643