title: Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer.
abstract: The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n=2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n=4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Spink
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bloom
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States; Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, United States.
authors.forename: Stewart
authors.initials: S
authors.lastname: Sell
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States; Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, United States.
authors.forename: Erasmus
authors.initials: E
authors.lastname: Schneider
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States; Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, United States; Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, United States.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ding
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States; Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, United States. Electronic address: spink@wadsworth.org.
authors.forename: David C
authors.initials: DC
authors.lastname: Spink
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human
keywords: (GGGGC)(n) repeat polymorphism; Aryl hydrocarbon receptor; Breast cancer; Colon cancer; Lung cancer; Short tandem repeat