title: N-methylpurine DNA glycosylase and OGG1 DNA repair activities: opposite associations with lung cancer risk.
abstract: Only a minority of smokers develop lung cancer, possibly due to genetic predisposition, including DNA repair deficiencies. To examine whether inter-individual variations in DNA repair activity of N-methylpurine DNA glycosylase (MPG) are associated with lung cancer, we conducted a blinded, population-based, case-control study with 100 lung cancer case patients and 100 matched control subjects and analyzed the data with conditional logistic regression. All statistical tests were two-sided. MPG enzyme activity in peripheral blood mononuclear cells from case patients was higher than in control subjects, results opposite that of 8-oxoguanine DNA glycosylase (OGG1) DNA repair enzyme activity. For lung cancer associated with one standard deviation increase in MPG activity, the adjusted odds ratio was 1.8 (95% confidence interval [CI] = 1.2 to 2.6; P = .006). A combined MPG and OGG1 activities score was more strongly associated with lung cancer risk than either activity alone, with an odds ratio of 2.3 (95% CI = 1.4 to 3.6; P < .001). These results form a basis for a future panel of risk biomarkers for lung cancer risk assessment and prevention.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Leitner-Dagan
authors.forename: Ziv
authors.initials: Z
authors.lastname: Sevilya
authors.forename: Mila
authors.initials: M
authors.lastname: Pinchev
authors.forename: Ran
authors.initials: R
authors.lastname: Kramer
authors.forename: Dalia
authors.initials: D
authors.lastname: Elinger
authors.forename: Laila C
authors.initials: LC
authors.lastname: Roisman
authors.forename: Hedy S
authors.initials: HS
authors.lastname: Rennert
authors.forename: Edna
authors.initials: E
authors.lastname: Schechtman
authors.forename: Laurence
authors.initials: L
authors.lastname: Freedman
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Zvi
authors.initials: Z
authors.lastname: Livneh
authors.forename: Tamar
authors.initials: T
authors.lastname: Paz-Elizur
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D016015:Logistic Models; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C076131:DNA-3-methyladenine glycosidase II