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Lung cancer risk and variation in MGMT activity and sequence

Lookup NU author(s): Dr Mauro Santibanez Koref


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O6-Alkylguanine-DNA alkyltransferase (MGMT) repairs DNA adducts that result from alkylation at the O6 position of guanine. These lesions are mutagenic and toxic and can be produced by a variety of agents including the tobacco-specific nitrosamines, carcinogens present in cigarette smoke. Here, we review some of our work in the context of inter-individual differences in MGMT expression and their potential influence on lung cancer risk. In humans there are marked inter-individual differences in not only levels of DNA damage in the lung (N7-methylguanine) that can arise from exposure to methylating agents but also in MGMT activity in lung tissues. In the presence of such exposure, this variability in MGMT activity may alter cancer susceptibility, particularly as animal models have demonstrated that the complete absence of MGMT activity predisposes to alkylating-agent induced cancer while overexpression is protective. Recent studies have uncovered a series of polymorphisms that affect protein activity or are associated with differences in expression levels. The associations between these (and other) polymorphisms and cancer risk are inconsistent, possibly because of small sample sizes and inter-study differences in lung cancer histology. We have recently analysed a consecutive series of case-control studies and found evidence that lung cancer risk was lower in subjects with the R178 allele. © 2007 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Povey AC, Margison GP, Santibanez-Koref MF

Publication type: Article

Publication status: Published

Journal: DNA Repair

Year: 2007

Volume: 6

Issue: 8

Pages: 1134-1144

ISSN (print): 1568-7864

ISSN (electronic): 1568-7856

Publisher: Elsevier BV


DOI: 10.1016/j.dnarep.2007.03.022


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