title: Significant interactions between maternal PAH exposure and single nucleotide polymorphisms in candidate genes on B[ a ]P-DNA adducts in a cohort of non-smoking Polish 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 known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[ a ]P metabolism genes on B[ a ]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking women ( n = 368) with available data on maternal PAH exposure, paired cord adducts, and genetic data who resided in Krakow, Poland. We selected eight common variants in maternal and newborn candidate genes related to B[ a ]P metabolism, detoxification, and repair for our analyses: CYP1A1 , CYP1A2 , CYP1B1 , GSTM1 , GSTT2 , NQO1 , and XRCC1 . We observed significant interactions between maternal PAH exposure and SNPs on cord B[ a ]P-DNA adducts in the following genes: maternal CYP1A1 and GSTT2 , and newborn CYP1A1 and CYP1B1 . These novel findings highlight differences in maternal and newborn genetic contributions to B[ a ]P-DNA adduct formation and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[ a ]P.
authors: Shoba
authors: S
authors: Iyer
authors: Department of Biostatistics , Mailman School of Public Health , Columbia University , New York , NY 10032 , USA.
authors: Ya
authors: Y
authors: Wang
authors: Department of Biostatistics , Mailman School of Public Health , Columbia University , New York , NY 10032 , USA.
authors: Wei
authors: W
authors: Xiong
authors: Deliang
authors: D
authors: Tang
authors: Former Chair of Epidemiology and Preventive Medicine , Jagiellonian University Medical College , Krakow 31-007 , Poland.
authors: Wieslaw
authors: W
authors: Jedrychowski
authors: National Cancer Institute , Gaithersburg , MD 20877 , USA and.
authors: Stephen
authors: S
authors: Chanock
authors: Department of Biostatistics , Mailman School of Public Health , Columbia University , New York , NY 10032 , USA.
authors: Shuang
authors: S
authors: Wang
authors: Laura
authors: L
authors: Stigter
authors: Chair of Epidemiology and Preventive Medicine , Jagiellonian University Medical College , Krakow 31-007 , Poland.
authors: Elzbieta
authors: E
authors: Mróz
authors: Frederica
authors: F
authors: Perera
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018736:DNA Adducts; D004781:Environmental Exposure; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D011044:Poland; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: D000393:Air Pollutants; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1