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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
Author(s) -
Mollerup Steen,
Berge Gisle,
Bæra Rita,
Skaug Vidar,
Hewer Alan,
Phillips David H.,
Stangeland Lodve,
Haugen Aage
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21891
Subject(s) - cyp1b1 , lung cancer , microsomal epoxide hydrolase , carcinogen , aryl hydrocarbon receptor , cytochrome p450 , lung cancer susceptibility , lung , medicine , gene , biology , gene expression , dna , epoxide hydrolase , endocrinology , microsome , enzyme , genotype , genetics , biochemistry , single nucleotide polymorphism , transcription factor
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 on 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 32 P‐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 lung cancer among females. © 2006 Wiley‐Liss, Inc.