Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer

• Published in: DNA repair Vol. 9; no. 5; pp. 558 - 566
• Main Authors: Zhang, Zhengdong, Wang, Luo, Wei, Sheng, Liu, Zhensheng, Wang, Li-E., Sturgis, Erich M., Wei, Qingyi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.05.2010; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Bacteriology; Base Sequence; Biological and medical sciences; Carcinogenesis; Case-Control Studies; Disease Progression; DNA Modification Methylases - genetics; DNA repair; DNA Repair - genetics; DNA Repair Enzymes - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetic susceptibility; Genotype; Growth, nutrition, cell differenciation; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Humans; Male; Medical sciences; Methylation; Microbiology; Middle Aged; Molecular and cellular biology; Molecular epidemiology; Molecular genetics; Mutagenesis. Repair; Oral cancer; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Polymorphism, Single Nucleotide; Tumor Suppressor Proteins - genetics; Tumors; Young Adult; Molecular epidemiology; Oral cancer; Genetic susceptibility; Methylation; DNA repair; Stomatology; Risk; Malignant tumor; Genetic determinism; Repair gene; Sensitivity; DNA; ENT disease; Head and neck cancer; Oral cavity disease; Repair; Cancer; Polymorphism
• ISSN: 1568-7864; 1568-7856; 1568-7856
• DOI: 10.1016/j.dnarep.2010.02.006

Methylating agents are involved in carcinogenesis, and the DNA repair protein O 6-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O 6-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.