Assessment of interactions between PAH exposure and genetic polymorphisms on PAH-DNA adducts in African American, Dominican, and Caucasian mothers and newborns.
Polycyclic aromatic hydrocarbons (PAH) are widespread pollutants commonly found in air, food, and drinking water. Benzo[a]pyrene is a well-studied representative PAH found in air from fossil fuel combustion and a transplacental carcinogen experimentally. PAHs bind covalently to DNA to form DNA adducts, an indicator of DNA damage, and an informative biomarker of potential cancer risk. Associations between PAH-DNA adduct levels and both cancer risk and developmental deficits have been seen in previous experimental and epidemiologic studies. Several genes have been shown to play an important role in the metabolic activation or detoxification of PAHs, including the cytochrome P450 genes CYP1A1 and CYP1B1 and the glutathione S-transferase (GST) genes GSTM1, and GSTT2. Genetic variation in these genes could influence susceptibility to adverse effects of PAHs in polluted air. Here, we have explored interactions between prenatal PAH exposure and 17 polymorphisms in these genes (rs2198843, rs1456432, rs4646903, rs4646421, rs2606345, rs7495708, rs2472299, rs162549, rs1056837, rs1056836, rs162560, rs10012, rs2617266, rs2719, rs1622002, rs140194, and gene deletion GSTM1-02) and haplotypes on PAH-DNA adducts in cord blood of 547 newborns and in maternal blood of 806 mothers from three different self-described ethnic groups: African Americans, Dominicans, and Caucasians. PAHs were measured by personal air monitoring of mothers during pregnancy. Significant interactions (p < 0.05) were observed between certain genetic polymorphisms and CYP1A1 haplotype and PAHs in mothers and their newborns in the three ethnic groups. However, with our limited sample size, the current findings are suggestive only, warranting further study.
Wang
Shuang
S
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Chanock
Stephen
S
Tang
Deliang
D
Li
Zhigang
Z
Jedrychowski
Wieslaw
W
Perera
Frederica P
FP
D000328:Adult; D001741:Black or African American; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood; D002273:Carcinogens / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts / Q000633:toxicity*; D004249:DNA Damage; D004781:Environmental Exposure; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D008297:Male; D008431:Maternal-Fetal Exchange; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D009519:New York City; D011044:Poland; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D044465:White People
D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor; D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts; D005982:Glutathione Transferase; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct; C585496:CYP1B1 protein, human; C491107:GSTT2 protein, human