Persistent organic pollutants and promoter hypermethylation of the O6-methylguanine-DNA methyltransferase gene
Abstract
Promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) DNA repair gene is important during carcinogenesis. We explored whether organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), were associated with hypermethylation of the MGMT gene promoter in peripheral leukocytes among 368 Koreans without cancer. Hypermethylation decreased as OCPs increased (Ptrend = 0.02), while PCB concentrations showed an inverted U-shaped association (Pquadratic < 0.01). The prevalence of MGMT promoter hypermethylation was highest within the 2nd quintile of the PCB summary score (28.4%), while it was only 2.7% in the upper 10% score. Chronic exposure to these chemicals may affect methylation of the MGMT promoter, with possibly non-monotonic dose response relationships.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In healthy Koreans, exposure to PCBs exhibits an inverted U-shape dose-response relationship with DNA methylation of the promoter region of the DNA repair gene, O6-methylguanin-DNA methyltransferase.
“For example, in healthy Koreans, exposure to PCBs exhibits an inverted U-shape dose–response relationship with DNA methylation of the promoter region of the DNA repair gene, O6-methylguanin-DNA methyltransferase [ 116 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [116]
Cites
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans
Zuckerman, A. J. (1995) · Journal of Clinical Pathology · doi:10.1136/jcp.48.7.691-a · Cited by 8,761 · see citing works
IARC monographs on the evaluation of carcinogenic risks to humans
Hopkins, J. C. A. (1989) · Food and Chemical Toxicology · doi:10.1016/0278-6915(89)90054-9 · Cited by 2,868 · see citing works
Esteller, M., Hamilton, S. R., Burger, P. C., Baylin, S. B., & Herman, J. G. (1999) · PubMed · Cited by 1,253 · see citing works
Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding
Phillips, D. L., Pirkle, J. L., Burse, V. W., Bernert, J. T., Henderson, L. O., & Needham, L. L. (1989) · Archives of Environmental Contamination and Toxicology · doi:10.1007/bf01055015 · Cited by 884 · see citing works
Lee, D., Lee, I., Song, K., Steffes, M. W., Toscano, W. A., Baker, B. A., & Jacobs, D. R. (2006) · Diabetes Care · doi:10.2337/dc06-0543 · Cited by 641 · see citing works
Self-citationRattan, S. I. S. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2007.03.002 · Cited by 498 · see citing works
Carcinogenicity of polychlorinated biphenyls and polybrominated biphenyls
Secretan, B., LOOMIS, D. P., Grosse, Y., Ghissassi, F. E., Bouvard, V., Benbrahim‐Tallaa, L., Guha, N., Baan, R. A., Mattock, H., & Straíf, K. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70104-9 · Cited by 454 · see citing works
Chlorinated Persistent Organic Pollutants, Obesity, and Type 2 Diabetes
Lee, D., Porta, M. S., Jacobs, D. R., & Vandenberg, L. N. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1084 · Cited by 420 · see citing works
Self-citationEpigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors
Herceg, Z. (2007) · Mutagenesis · doi:10.1093/mutage/gel068 · Cited by 371 · see citing works
Rusiecki, J. A., Baccarelli, A., Bollati, V., Tarantini, L., Moore, L. E., & Bonefeld-Jorgensen, E. C. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11338 · Cited by 352 · see citing works
Low Dose of Some Persistent Organic Pollutants Predicts Type 2 Diabetes: A Nested Case–Control Study
Lee, D., Steffes, M. W., Sjödin, A., Jones, R. S., Needham, L. L., & Jacobs, D. R. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.0901480 · Cited by 347 · see citing works
Self-citationChristmann, M., Verbeek, B., Roos, W. P., & Kaina, B. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2011.06.002 · Cited by 242 · see citing works
Dumenco, L. L., Allay, E. R., Norton, K., & Gerson, S. L. (1993) · Science · doi:10.1126/science.8421782 · Cited by 236 · see citing works
Calabrese, E. J. (2005) · Critical Reviews in Toxicology · doi:10.1080/10408440591034502 · Cited by 213 · see citing works
Optimizing methodologies for PCR-based DNA methylation analysis
Hernández, H. G., Tse, M. Y., Pang, S. C.-N., Arboleda, H., & Forero, D. A. (2013) · BioTechniques · doi:10.2144/000114087 · Cited by 172 · see citing works
MGMT hypermethylation: A prognostic foe, a predictive friend
Jacinto, F. V., & Esteller, M. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.03.013 · Cited by 158 · see citing works
Zaidi, N. H., Pretlow, T. P., O’Riordan, M. A., Dumenco, L. L., Allay, E. R., & Gerson, S. L. (1995) · Carcinogenesis · doi:10.1093/carcin/16.3.451 · Cited by 133 · see citing works
Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice.
Sakumi, K., Shiraishi, A., Shimizu, S., Tsuzuki, T., Ishikawa, T., & Sekiguchi, M. (1997) · PubMed · Cited by 131 · see citing works
Strong associations between low-dose organochlorine pesticides and type 2 diabetes in Korea
Son, H.-K., Kim, S., Kang, J., Chang, Y., Park, S.-K., Lee, S., Jacobs, D. R., & Lee, D.-H. (2010) · Environment International · doi:10.1016/j.envint.2010.02.012 · Cited by 120 · see citing works
Self-citationFukushima, S., Kakehashi, A., Puatanachokchai, R., Kushida, M., Wanibuchi, H., & Morimura, K. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi160 · Cited by 100 · see citing works
Effects of age, sex, and persistent organic pollutants on DNA methylation in children
Huen, K., Yousefi, P., Bradman, A., Yan, L., Harley, K. G., Kogut, K. R., Eskenazi, B., & Holland, N. (2013) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21845 · Cited by 97 · see citing works
Lind, L., Penell, J., Luttropp, K., Nordfors, L., Syvänen, A.-C., Axelsson, T., Salihovic, S., van Bavel, B., Fall, T., Ingelsson, E., et al. (2013) · Environment International · doi:10.1016/j.envint.2013.07.008 · Cited by 94 · see citing works
Becker, K., Dösch, J., Gregel, C. M., Martin, B. A., & Kaina, B. (1996) · PubMed · Cited by 89 · see citing works
Golden, R. J., & Kimbrough, R. D. (2009) · Critical Reviews in Toxicology · doi:10.1080/10408440802291521 · Cited by 70 · see citing works
Carcinogenic effects of polychlorinated biphenyls
FAROON, O. M., Keith, S., Jones, D. E., & Rosa, C. T. D. (2001) · Toxicology and Industrial Health · doi:10.1191/0748233701th098oa · Cited by 61 · see citing works
Park, S.-K., Son, H.-K., Lee, S.-K., Kang, J. H., Chang, Y., Jacobs, D. R., & Lee, D. (2010) · Journal of Preventive Medicine and Public Health · doi:10.3961/jpmph.2010.43.1.1 · Cited by 57 · see citing works
Self-citationEffects of Persistent and Bioactive Organic Pollutants on Human Health
(2013) · Wiley eBooks · doi:10.1002/9781118679654 · Cited by 53 · see citing works
Aberrant DNA methylation profiles of non-small cell lung cancers in a Korean population
Kim, D. S., Ick, S., Lee, J., Lee, Y., Choi, J. E., Kim, M., Lim, J., Lee, E. B., Kim, C., Park, T. I., et al. (2007) · Lung Cancer · doi:10.1016/j.lungcan.2007.04.008 · Cited by 52 · see citing works
Self-citationPersistent toxic substances: sources, fates and effects
Wong, M. H., Armour, M., Naidu, R., & Man, M. (2012) · Reviews on Environmental Health · doi:10.1515/reveh-2012-0040 · Cited by 48 · see citing works
Sukata, T., Uwagawa, S., Ozaki, K., Ogawa, M., Nishikawa, T., Iwai, S., Kakehashi, A., Wanibuchi, H., Imaoka, S., Funae, Y., et al. (2002) · International Journal of Cancer · doi:10.1002/ijc.10312 · Cited by 47 · see citing works
Potential Human Cancer Risks from Exposure to PCBs: A Tale of Two Evaluations
Golden, R. J., Doull, J., Waddell, W. J., & Mandel, J. S. (2003) · Critical Reviews in Toxicology · doi:10.1080/10408440390242414 · Cited by 46 · see citing works
Mortality of workers employed at organochlorine pesticide manufacturing plants--an update.
Brown, D. P. (1992) · Scandinavian Journal of Work Environment & Health · doi:10.5271/sjweh.1593 · Cited by 42 · see citing works
Lee, D., & Jacobs, D. R. (2014) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2014-203861 · Cited by 41 · see citing works
Self-citationKristensen, L. S., Raynor, M. P., Candiloro, I. L. M., & Dobrovic, A. (2012) · Oncotarget · doi:10.18632/oncotarget.480 · Cited by 38 · see citing works
Adverse health effects of environmental chemical agents through non-genotoxic mechanisms: Figure 1
Henkler, F., & Luch, A. (2010) · Journal of Epidemiology & Community Health · doi:10.1136/jech.2008.083881 · Cited by 34 · see citing works
Human contamination by environmental chemical pollutants: Can we assess it more properly?
Porta, M. S. (2012) · Preventive Medicine · doi:10.1016/j.ypmed.2012.09.020 · Cited by 22 · see citing works
Self-citationCancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up
van Amelsvoort, L. G. P. M., Slangen, J. J. M., Tsai, S. P., de Jong, G., & Kant, I. (2008) · International Archives of Occupational and Environmental Health · doi:10.1007/s00420-008-0325-1 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations
Martin, E. M., & Fry, R. C. (2018) · Annual Review of Public Health · doi:10.1146/annurev-publhealth-040617-014629 · Cited by 640 · see citing works
Keil, K. P., & Lein, P. J. (2016) · Environmental Epigenetics · doi:10.1093/eep/dvv012 · Cited by 167 · see citing works
Goodman, S. J., Chappell, G. A., Guyton, K. Z., Pogribny, I. P., & Rusyn, I. (2021) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2021.108408 · Cited by 36 · see citing works
Shan, A., Li, M., Li, X., Li, Y., Yan, M., Xian, P., Chang, Y., Chen, X., & Tang, N. (2019) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.8b00312 · Cited by 27 · see citing works
Park, E. Y., Kim, J., Park, E., Oh, J., Kim, B., & Lim, M. K. (2021) · Chemosphere · doi:10.1016/j.chemosphere.2021.129596 · Cited by 22 · see citing works
Rohr, P., Karen, S., Francisco, L. F. V., de Oliveira, M. A., Neto, M. F. D. S., & Silveira, H. C. S. (2024) · Current Zoology · doi:10.1093/eep/dvae005 · Cited by 19 · see citing works
Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey
Pittman, G. S., Wang, X., Campbell, M. R., Coulter, S. J., Olson, J. R., Pavúk, M., Birnbaum, L. S., & Bell, D. A. (2019) · Epigenetics · doi:10.1080/15592294.2019.1666654 · Cited by 16 · see citing works
Dioxin-like compound exposures and DNA methylation in the Anniston Community Health Survey Phase II
Pittman, G. S., Wang, X., Campbell, M. R., Coulter, S. J., Olson, J. R., Pavúk, M., Birnbaum, L. S., & Bell, D. A. (2020) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2020.140424 · Cited by 10 · see citing works
Lee, J.-Y., Lee, K. M., Lee, D. H., & Kim, D. S. (2017) · Biomarkers · doi:10.1080/1354750x.2017.1417482 · Cited by 7 · see citing works
Self-citationChen, G., Huang, T., Dai, Y., Huo, X., & Xu, X. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.117705 · Cited by 3 · see citing works
Tuminello, S., Durmuş, N., Snuderl, M., Chen, Y., Shao, Y., Reibman, J., Arslan, A. A., & Taioli, E. (2024) · Biomolecules · doi:10.3390/biom14101302 · Cited by 2 · see citing works
- Authors
- Park, S. Y., Kim, K.-S., Lee, Y.-M., Kim, M.-J., Jacobs, D. R., Porta, M., Kim, D.-S., & Lee, D.-H.
- Affiliations
- Kyungpook National University (KR)
- Department of Preventive Medicine and
- University of Minnesota (US)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Kim, Dong-Sun
- Lee, Duk-Hee
- Venue
- Biomarkers
- Publisher
- Informa UK Limited
- Published
- 2015-01-14
- Volume
- 20
- Issue
- 2
- Pages
- 136-142
- ISSN
- 1354-750X (ISSN-L)
- 1366-5804
- OpenAlex
- W2044251431
- Cited by
- 11
- References
- 37
- Citations by year
- 2025: 1 · 2024: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomarkers (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- persistent organic pollutants, MGMT promoter hypermethylation, O6-methylguanine-DNA methyltransferase, organochlorine pesticides, polychlorinated biphenyls, DNA methylation, peripheral blood leukocytes, non-monotonic dose-response, carcinogenesis, epigenetic biomarkers, Korean adults
- MeSH terms
- Environmental Pollutants, Humans, Hydrocarbons, Chlorinated, Gas Chromatography-Mass Spectrometry, Middle Aged, Pesticides, Polychlorinated Biphenyls, Promoter Regions, Genetic, Surveys and Questionnaires, Logistic Models, Case-Control Studies, Polymerase Chain Reaction, DNA Methylation, O(6)-Methylguanine-DNA Methyltransferase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
