Abstract 2753: Interactions between PAH exposure and genetic polymorphisms on BaP-DNA adducts in a NYC cohort of African American and Dominican 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 haplotype frequency in genes related to PAH metabolism and detoxification, and explored the interactions between PAH exposure and haplotype 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 African American (AA) and Dominican (D) mothers and newborns in New York City. WBC DNA was isolated from cord blood, and genetic polymorphisms and BaP-DNA cord adducts were then measured in 516 mothers and 323 newborns. Maternal PAH exposure was measured during pregnancy with a personal air exposure monitor. A total of 18 genes, selected for biologic relevance, were analyzed for SNPs. For this study, a subset of 7 maternal and newborn genes related to PAH metabolism, detoxification and repair were selected for haplotype analyses: CYP1A1, CYP1A2, CYP1B1, GSTM, GSTT, NQO1 and XRCC. Haplotype × PAH interactions on logarithmic-transformed BaP-DNA adduct levels were explored. Results: Notable differences in haplotype frequency were observed between AAs and Ds and between mothers and newborns. We observed a number of significant interactions between high PAH exposure and polymorphic haplotypes in both mothers and newborns on BaP-DNA adducts in cord blood. To give one example, the haplotype CACGCG of CYP1B1 in AA mothers had a frequency of 10.4%, versus 0.3% in D mothers (p<0.0001). By comparison, the reference haplotype TAGCTG had a frequency of 19.9%. We observed a significant interaction between the CYP1B1 haplotype and high PAH exposure on cord BaP-DNA adducts in AA newborns (β=−0.67, p=0.01) but not Ds (β=−0.13, p=0.72). We will present results for both maternal and newborn CYP1A1, CYP1A2, GSTM, GSTT, NQO1 and XRCC haplotypes in both AAs and Ds. Discussion: It is biologically plausible that an individual's ability to metabolically activate and detoxify BaP and repair DNA damage plays a role in susceptibility to DNA adduct formation following prenatal PAH exposure. Ultimately, this susceptibility could correlate with future risk of cancer development. We have identified haplotype patterns that differ between ethnic groups and also between mothers and newborns. We also observed several haplotype × PAH exposure interactions on cord BaP-DNA adducts, supporting 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 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2753. doi:10.1158/1538-7445.AM2011-2753