Carcinogenesis, Vol 18, 1285-1289, Copyright © 1997 by Oxford University Press
D Ryberg, V Skaug, A Hewer, DH Phillips, LW Harries, CR Wolf, D Ogreid, A Ulvik, P Vu and A Haugen
The A-G polymorphism at codon 104 in the glutathione S-transferase P1
(GSTP1) gene was examined in 138 male lung cancer patients and 297 healthy
controls. The patients had significantly higher frequency of the GG
genotype (15.9%) and a lower frequency of AA (38.4%) than the controls
(9.1% and 51.5%, respectively). The level of hydrophobic DNA- adducts were
determined in lung tissue from 70 current smokers. Patients with the GG
genotype had a significantly higher adduct level than patients with AA
(15.5 +/- 10.2 vs 7.9 +/- 5.1 per 10(8) nucleotides, P = 0.006). We also
analyzed the deletion polymorphism in the GSTM1 gene in 135 male patients
and 342 controls. The patients were stratified according to histology,
smoking dose, age, adduct level and mutational types found in the tumors
(Ki-ras and p53 genes). The results consistently indicated that the GSTM1
null genotype was associated with a slightly increased lung cancer risk.
When the combined GST M1 and P1 genotypes were examined, patients with the
combination null and AG or GG had significantly higher adduct levels than
all other genotype combinations (P = 0.011). The distribution of combined
genotypes was also significantly different in cases and controls, mainly
due to increased frequency of the combination GSTM1 null and GSTP1 AG or GG
among patients.
ARTICLES
Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
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