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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){sub 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){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, asmore » 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){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung cancer patients was 8-fold higher than in neonates • The (GGGGC){sub 2} allele may be associated with lung cancer susceptibility.« less

Authors:
 [1];  [2];  [1]; ;  [1];  [1]
  1. Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States)
  2. Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States)
Publication Date:
OSTI Identifier:
22439939
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 282; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; DNA; GENES; HUMAN POPULATIONS; LARGE INTESTINE; LUCIFERASE; LUNGS; MAMMARY GLANDS; NEONATES; NEOPLASMS; NEW YORK; PATIENTS; POLYCYCLIC AROMATIC HYDROCARBONS; PRIMATES; PYRENE; RECEPTORS; SPECIFICITY

Citation Formats

Spink, Barbara C., Bloom, Michael S., Wu, Susan, Sell, Stewart, Schneider, Erasmus, Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Ding, Xinxin, Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Spink, David C., E-mail: spink@wadsworth.org, and Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2014.10.017.
Spink, Barbara C., Bloom, Michael S., Wu, Susan, Sell, Stewart, Schneider, Erasmus, Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Ding, Xinxin, Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Spink, David C., E-mail: spink@wadsworth.org, & Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer. United States. https://doi.org/10.1016/J.TAAP.2014.10.017
Spink, Barbara C., Bloom, Michael S., Wu, Susan, Sell, Stewart, Schneider, Erasmus, Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Ding, Xinxin, Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201, Spink, David C., E-mail: spink@wadsworth.org, and Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201. 2015. "Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer". United States. https://doi.org/10.1016/J.TAAP.2014.10.017.
@article{osti_22439939,
title = {Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer},
author = {Spink, Barbara C. and Bloom, Michael S. and Wu, Susan and Sell, Stewart and Schneider, Erasmus and Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 and Ding, Xinxin and Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 and Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 and Spink, David C., E-mail: spink@wadsworth.org and Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201},
abstractNote = {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){sub 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){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 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){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung cancer patients was 8-fold higher than in neonates • The (GGGGC){sub 2} allele may be associated with lung cancer susceptibility.},
doi = {10.1016/J.TAAP.2014.10.017},
url = {https://www.osti.gov/biblio/22439939}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 282,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2015},
month = {Thu Jan 01 00:00:00 EST 2015}
}