Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients.
The levels of aromatic/hydrophobic DNA adducts were analyzed in normal lung tissue from 63 lung cancer patients and examined in relation to exposure and genetic factors. Adduct levels were significantly higher in smokers than in nonsmokers, but among smokers the number of cigarettes smoked per day had only low significance for the variation in adduct levels. An inverse correlation was found between years of smoking and DNA adduct levels (r = 0.52, P = 0.001). Thus, patients with high adduct levels generally had shorter duration of smoking and/or lower smoking dose before the clinical onset of the disease, which fits expected behavior of cancer susceptible individuals. The data indicated an excess of individuals with glutathione S-transferase M1 deficiency among male patients with high adduct levels. Among females the DNA adduct levels were higher than in males when adjusted for smoking dose. There was a highly significant difference in the distribution of males and females when smokers were divided into quartile groups according to adducts per pack year (trend test: 2-sided P = 0.005). This may indicate that women are at greater risk of tobacco-induced lung cancer.
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
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Ryberg
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Hewer
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Phillips
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Haugen
D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics*; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D004198:Disease Susceptibility; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics*; D008297:Male; D012044:Regression Analysis; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
D018736:DNA Adducts; D005982:Glutathione Transferase