title: Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns.
abstract: Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene-environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P.
authors.affiliation: Columbia Center for Children's Environmental Health and.
authors.forename: Shoba
authors.initials: S
authors.lastname: Iyer
authors.forename: Frederica
authors.initials: F
authors.lastname: Perera
authors.forename: Bingzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Deliang
authors.initials: D
authors.lastname: Tang
mesh_terms: D001741:Black or African American / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D015331:Cohort Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts / Q000097:blood / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004293:Dominican Republic / Q000208:ethnology; D005260:Female; D005312:Fetal Blood; D005982:Glutathione Transferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D009519:New York City / Q000208:ethnology; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012907:Smoking; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C585496:CYP1B1 protein, human; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C483009:GSTM3 protein, human; D005982:Glutathione Transferase