Cancer Epidemiology Biomarkers & Prevention, Vol 7, Issue 4 309-314, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Reduced expression of hMLH1 and hGTBP/hMSH6: a risk factor for head and neck cancer [published erratum appears in Cancer Epidemiol Biomarkers Prev 1998 Sep;7(9):841]

Q Wei, SA Eicher, Y Guan, L Cheng, J Xu, LN Young, KC Saunders, H Jiang, WK Hong, MR Spitz and SS Strom
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. qwei@request.mda.uth.tmc.edu

Head and neck cancer, like lung cancer, is considered a paradigm of an environmentally induced disease. Genetically determined variation in DNA repair capacity is thought to contribute to susceptibility to tobacco-related cancers. In this molecular epidemiology study, we investigated the association between DNA mismatch-repair (MMR) gene expression and the risk of head and neck cancer. Using our newly developed multiplex reverse transcription-PCR assay, we simultaneously evaluated the relative expression levels of five MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hGTBP/hMSH6) in the peripheral blood lymphocytes of 78 patients (mean age = 59.6 +/- 12.4 years) with newly diagnosed head and neck cancer and 86 healthy controls (mean age = 58.2 +/- 12.9 years). The relative MMR gene expression was not correlated with disease stage or tumor site in the cases or with smoking and alcohol use in the controls. The expression levels increased with age in both cases and controls, but the mean expression of hMLH1, hPMS1, and hGTBP/hMSH6 was significantly lower in the cases than in the controls (P < 0.05). Using the median expression level in controls as the cutoff value, significantly increased odds ratios (ORs) were associated only with low expression of hMLH1 (OR = 4.4; 95% confidence interval = 2.1-9.1) and hGTBP/hMSH6 (OR = 2.1; 95% confidence interval = 1.1-4.1) after adjustment for age, sex, ethnicity, smoking status, and alcohol use. The results suggest that low hMLH1 and hGTBP/hMSH6 expression is associated with an increased risk of head and neck cancer. Additional studies with a larger number of subjects are warranted to confirm these findings.

This article has been cited by other articles:

				K. L. Lockett, M.C. Hall, P. E. Clark, S.-C. Chuang, B. Robinson, H.-Y. Lin, L.J. Su, and J. J. Hu DNA damage levels in prostate cancer cases and controls Carcinogenesis, June 1, 2006; 27(6): 1187 - 1193. [Abstract] [Full Text] [PDF]

				J. Gu, M. R. Spitz, H. Zhao, J. Lin, H.B. Grossman, C. P. Dinney, and X. Wu Roles of tumor suppressor and telomere maintenance genes in cancer and aging--an epidemiological study Carcinogenesis, October 1, 2005; 26(10): 1741 - 1747. [Abstract] [Full Text] [PDF]

				M. R. Spitz, Q. Wei, Q. Dong, C. I. Amos, and X. Wu Genetic Susceptibility to Lung Cancer: The Role of DNA Damage and Repair Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 689 - 698. [Full Text] [PDF]

				W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani Polymorphisms in the DNA Repair Genes XRCC1 and ERCC2, Smoking, and Lung Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2003; 12(4): 359 - 365. [Abstract] [Full Text] [PDF]

				T. Hanaoka, Y. Yamano, H. Hashimoto, J. Kagawa, and S. Tsugane A Preliminary Evaluation of Intra- and Interindividual Variations of hOGG1 Messenger RNA Levels in Peripheral Blood Cells as Determined by a Real-Time Polymerase Chain Reaction Technique Cancer Epidemiol. Biomarkers Prev., November 1, 2000; 9(11): 1255 - 1258. [Abstract] [Full Text]

				Qingyi Wei, Lie Cheng, C. I. Amos, L.-E. Wang, Zhaozheng Guo, W. K. Hong, and M. R. Spitz Repair of Tobacco Carcinogen-Induced DNA Adducts and Lung Cancer Risk: a Molecular Epidemiologic Study J Natl Cancer Inst, November 1, 2000; 92(21): 1764 - 1772. [Abstract] [Full Text] [PDF]

				S. E. Berry, T. W. Davis, J. E. Schupp, H.-S. Hwang, Niels de Wind, and T. J. Kinsella Selective Radiosensitization of Drug-resistant MutS Homologue-2 (MSH2) Mismatch Repair-deficient Cells by Halogenated Thymidine (dThd) Analogues: Msh2 Mediates dThd Analogue DNA Levels and the Differential Cytotoxicity and Cell Cycle Effects of the dThd Analogues and 6-Thioguanine Cancer Res., October 1, 2000; 60(20): 5773 - 5780. [Abstract] [Full Text]

				G. Xinarianos, T. Liloglou, W. Prime, P. Maloney, J. Callaghan, P. Fielding, J. R. Gosney, and J. K. Field hMLH1 and hMSH2 Expression Correlates with Allelic Imbalance on Chromosome 3p in Non-Small Cell Lung Carcinomas Cancer Res., August 1, 2000; 60(15): 4216 - 4221. [Abstract] [Full Text]

				M. Berwick and P. Vineis Markers of DNA Repair and Susceptibility to Cancer in Humans: an Epidemiologic Review J Natl Cancer Inst, June 7, 2000; 92(11): 874 - 897. [Abstract] [Full Text] [PDF]

				E. M. Sturgis, E. J. Castillo, L. Li, R. Zheng, S. A. Eicher, G. L. Clayman, S. S. Strom, M. R. Spitz, and Q. Wei Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck Carcinogenesis, November 1, 1999; 20(11): 2125 - 2129. [Abstract] [Full Text] [PDF]

				L. Cheng, Y. Guan, L. Li, R. J. Legerski, J. Einspahr, J. Bangert, D. S. Alberts, and Q. Wei Expression in Normal Human Tissues of Five Nucleotide Excision Repair Genes Measured Simultaneously by Multiplex Reverse Transcription-Polymerase Chain Reaction Cancer Epidemiol. Biomarkers Prev., September 1, 1999; 8(9): 801 - 807. [Abstract] [Full Text]

				C. Matthias, V. Jahnke, P. W. Jones, P. R. Hoban, J. E. Alldersea, S. F. Worrall, A. A. Fryer, and R. C. Strange Cyclin D1, Glutathione S-Transferase, and Cytochrome P450 Genotypes and Outcome in Patients with Upper Aerodigestive Tract Cancers: Assessment of the Importance of Individual Genes Using Multivariate Analysis Cancer Epidemiol. Biomarkers Prev., September 1, 1999; 8(9): 815 - 823. [Abstract] [Full Text]

				E. M. Sturgis, G. L. Clayman, Y. Guan, Z. Guo, and Q. Wei DNA Repair in Lymphoblastoid Cell Lines From Patients With Head and Neck Cancer Arch Otolaryngol Head Neck Surg, February 1, 1999; 125(2): 185 - 190. [Abstract] [Full Text] [PDF]

				D. K. Chang, L. Ricciardiello, A. Goel, C. L. Chang, and C. R. Boland Steady-state Regulation of the Human DNA Mismatch Repair System J. Biol. Chem., June 9, 2000; 275(24): 18424 - 18431. [Abstract] [Full Text] [PDF]