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

Publication ,  Journal Article
Zhang, Z; Wang, L; Wei, S; Liu, Z; Wang, L-E; Sturgis, EM; Wei, Q
Published in: DNA Repair (Amst)
May 4, 2010

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.

Duke Scholars

Published In

DNA Repair (Amst)

DOI

EISSN

1568-7856

Publication Date

May 4, 2010

Volume

9

Issue

5

Start / End Page

558 / 566

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Tumor Suppressor Proteins
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Head and Neck Neoplasms
  • Genotype
  • Genetic Predisposition to Disease
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, Z., Wang, L., Wei, S., Liu, Z., Wang, L.-E., Sturgis, E. M., & Wei, Q. (2010). Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer. DNA Repair (Amst), 9(5), 558–566. https://doi.org/10.1016/j.dnarep.2010.02.006
Zhang, Zhengdong, Luo Wang, Sheng Wei, Zhensheng Liu, Li-E Wang, Erich M. Sturgis, and Qingyi Wei. “Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer.DNA Repair (Amst) 9, no. 5 (May 4, 2010): 558–66. https://doi.org/10.1016/j.dnarep.2010.02.006.
Zhang Z, Wang L, Wei S, Liu Z, Wang L-E, Sturgis EM, et al. Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer. DNA Repair (Amst). 2010 May 4;9(5):558–66.
Zhang, Zhengdong, et al. “Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer.DNA Repair (Amst), vol. 9, no. 5, May 2010, pp. 558–66. Pubmed, doi:10.1016/j.dnarep.2010.02.006.
Zhang Z, Wang L, Wei S, Liu Z, Wang L-E, Sturgis EM, Wei Q. Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer. DNA Repair (Amst). 2010 May 4;9(5):558–566.
Journal cover image

Published In

DNA Repair (Amst)

DOI

EISSN

1568-7856

Publication Date

May 4, 2010

Volume

9

Issue

5

Start / End Page

558 / 566

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Tumor Suppressor Proteins
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Head and Neck Neoplasms
  • Genotype
  • Genetic Predisposition to Disease
  • Female