Genetic association and functional studies of major polymorphic variants of MGMT

James M. Bugni, Jiali Han, Miaw sheue Tsai, David J. Hunter, Leona D. Samson

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The DNA repair protein, O6-methylguanine DNA-methyltransferase (MGMT) prevents mutations and cell death that result from aberrant alkylation of DNA. The polymorphic variants Leu84Phe, Ile143Val, and Lys178Arg are frequent in the human population. We review here studies of these and other MGMT polymorphisms and their association with risk for lung, breast, colorectal and endometrial cancer with a consideration of gene-environment interactions. In addition, we review studies of the effects of polymorphic variation on alkyltransferase activity and expression. It is formally possible that polymorphic variation could modify functions of MGMT other than its alkyltransferase activity. While it was previously reported that an alkylated form of MGMT modifies Estrogen Receptor alpha activity, from our studies we conclude that this regulation is not a major function of MGMT. Overall, the effects of polymorphic variation on protein function are subtle, and further investigation is required to provide a comprehensive mechanism that explains the observed associations of these variants with risk for cancer.

Original languageEnglish (US)
Pages (from-to)1116-1126
Number of pages11
JournalDNA Repair
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Methyltransferases
Genetic Association Studies
Association reactions
DNA
Alkyl and Aryl Transferases
Gene-Environment Interaction
Estrogen Receptor alpha
Alkylation
Endometrial Neoplasms
DNA Repair
Cell death
Polymorphism
Colorectal Neoplasms
Lung Neoplasms
Proteins
Cell Death
Breast Neoplasms
Repair
Genes
Mutation

Keywords

  • Cancer
  • O-methylguanine DNA-methyltransferase
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Genetic association and functional studies of major polymorphic variants of MGMT. / Bugni, James M.; Han, Jiali; Tsai, Miaw sheue; Hunter, David J.; Samson, Leona D.

In: DNA Repair, Vol. 6, No. 8, 01.08.2007, p. 1116-1126.

Research output: Contribution to journalArticle

Bugni, James M. ; Han, Jiali ; Tsai, Miaw sheue ; Hunter, David J. ; Samson, Leona D. / Genetic association and functional studies of major polymorphic variants of MGMT. In: DNA Repair. 2007 ; Vol. 6, No. 8. pp. 1116-1126.
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