title: O6-Alkylguanine-DNA-alkyltransferase activity in peripheral leukocytes, smoking and risk of lung cancer.
abstract: The level of activity of O6-alkylguanine-DNA-alkyltransferase (AGT), a DNA repair enzyme, in blood lymphocytes may be a marker of susceptibility to lung cancer. We measured the AGT activity level, expressed as pmoles of repaired bases/mg protein, in leukocytes of 153 lung cancer cases (of whom 80 were never smokers) and 106 controls (76 never smokers) enrolled in eight centres from seven countries. Subjects were interviewed with respect to active smoking and exposure to environmental tobacco smoke (ETS). Among never smokers, the odds ratios (ORs) of lung cancer were 1.3 (95% confidence interval 0.5-3.9), 1.5 (0.6-4.1) and 1.4 (0.5-3.8) in quartiles of decreasing AGT activity level, as compared to the upper quartile (P value of test for linear trend 0.6). Corresponding ORs among smokers were 3.4 (0.9-13), 2.0 (0.5-8.3) and 0.4 (0.1-1.6) (P value of test for linear trend 0.4). No interaction was suggested between AGT activity level and either cumulative smoking or exposure to ETS. Reduced AGT activity was not clearly associated with increased lung cancer risk in either smokers or non-smokers. However, the small size of our study argues for a prudent interpretation of our results.
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert-Thomas, Lyon, France. boffetta@iarc.fr
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.forename: Anush
authors.initials: A
authors.lastname: Mukeria
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Vali
authors.initials: V
authors.lastname: Constantinescu
authors.forename: Halina
authors.initials: H
authors.lastname: Batura-Gabryel
authors.forename: Irene
authors.initials: I
authors.lastname: Brüske-Hohlfeld
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schmid
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Simonato
authors.forename: Päivi
authors.initials: P
authors.lastname: Pelkonen
authors.forename: Janet
authors.initials: J
authors.lastname: Hall
mesh_terms: D000368:Aged; D002273:Carcinogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000494:pharmacology*; D016017:Odds Ratio; D012907:Smoking
chemical_list: D002273:Carcinogens; D019853:O(6)-Methylguanine-DNA Methyltransferase