Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer |
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| Authors: | Zhengdong Zhang Luo Wang Sheng Wei Zhensheng Liu Li-E. Wang Erich M. Sturgis Qingyi Wei |
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| Affiliation: | 1. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States;2. Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States;3. Program in Human and Molecular Genetics, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, United States;1. Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, 1 University Place, Rensselaer, NY 12144, USA;2. Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, USA;3. Institute for Health and the Environment, University at Albany, State University of New York, Rensselaer, NY, USA;4. New York State Cancer Registry, New York State Department of Health, Albany, NY, USA;5. Department of Educational and Counseling Psychology, School of Education, University at Albany, State University of New York, Albany, NY, USA;6. Health Department, Environmental Health Center, Cluj-Napoca, Romania;7. Department of Environmental Epidemiology, National Institute of Environmental Health, Budapest, Hungary;8. Department of Environmental Health, Regional Authority of Public Health, Banska Bystrica, Slovakia;9. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;10. Department of Social and Environmental Health Research, Public Health, London School of Hygiene and Tropical Medicine, London, UK;11. Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, UK;12. Institut für Chemie-Analytische Chemie, Karl-Franzens-Universität, Graz, Austria;13. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany;1. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;2. Comprehensive Genetic Center, Hope Generation Foundation, Tehran, Iran;3. Gene Clinic, Tehran, Iran;4. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA;2. Department of Biomedical Informatics, Stanford University, Stanford, CA 94305, USA;3. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD 21205, USA;4. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA;5. Institute of Aging Research, Guangdong Medical College, Dongguan, China;1. Department of Pharmacy Practice, Qassim University, Saudi Arabia;2. Department of Pharmacy, University of Huddersfield, Huddersfield, UK;3. School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia |
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| Abstract: | Methylating agents are involved in carcinogenesis, and the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O6-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case–control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C > T and 16286C > T and two in the promoter region, 45996G > T and 46346C > A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT + TT, and 46346CA + AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) = 1.05–1.53). This increased risk was also more pronounced among young subjects (OR = 1.81; 95% CI = 1.11–2.96), men (OR = 1.24; 95% CI = 1.00–1.55), ever smokers (OR = 1.25; 95% = 1.01–1.56), ever drinkers (OR = 1.29; 95% CI = 1.04–1.60), patients with oropharyngeal cancer (OR = 1.45; 95% CI = 1.12–1.87), and oropharyngeal cancer with regional lymph node metastasis (OR = 1.52; 95% CI = 1.16–1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites. |
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