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Sex differences in risk of lung cancer: Expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts

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Date
2006-08-15
ICR Author
Phillips, David Hunter
Author
Mollerup, S
Berge, G
Baera, R
Skaug, V
Hewer, A
Phillips, DH
Stangeland, L
Haugen, A
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Type
Journal Article
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Abstract
It is controversial whether women have a higher lung cancer susceptibility compared to men. We previously reported higher levels of smoking-related bulky DNA adducts in female lungs. In a pilot study (27 cases), we also found a higher level of female lung cytochrome P4501A1 (CYP1A1) gene expression. In the present extended study we report oil the pulmonary expression of several genes involved in polycyclic aromatic hydrocarbon bioactivation in relation to sex, smoking and DNA adducts. CYP1A1, CYP1B1, aryl hydrocarbon receptor and microsomal epoxide hydrolase gene expression was measured by quantitative real-time reverse transcriptase-PCR in 121 normal lung tissue samples. The expression of CYP1A1 and CYP1B1 was significantly higher among current smokers compared to ex-smokers and never-smokers. Among current smokers, females had a 3.9-fold higher median level of CYP1A1 compared to males (p = 0.011). CYP1B1 expression was not related to sex. Lung DNA adducts (measured by P-32-postlabeling) were highly significantly related to CYP1A1 (P < 0.0001) irrespective of smoking-status. Our results are consistent with the hypothesis that CYP1A1 plays a significant role in lung DNA adduct formation and support a higher susceptibility to long cancer among females. (c) 2006 Wiley-Liss, Inc.
URI
https://repository.icr.ac.uk/handle/internal/2515
DOI
https://doi.org/10.1002/ijc.21891
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  • Closed Research Teams
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Human Biomonitoring & Carcinogen Activation
Language
eng
License start date
2006-08-15
Citation
INTERNATIONAL JOURNAL OF CANCER, 2006, 119 pp. 741 - 744
Publisher
WILEY-LISS

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