Smoking-related gene expression in laser capture-microdissected human lung

Xiang Lin Tan, Tao Wang, Shengli Xiong, Shalini V. Kumar, Weiguo Han, Simon D. Spivack

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Interindividual differences in quantitative expression could underlie a propensity for lung cancer. To determine precise individual gene expression signatures on a lung compartment-specific basis, we investigated the expression of carcinogen metabolism genes encoding cytochromes P450 (CYP) 1B1, 2A13, GSTP1, and a tumor suppressor gene p16 in laser capture-microdissected samples of human alveolar compartment (AC) and bronchial epithelial compartment (BEC) lung tissue from 62 smokers and nonsmokers. Experimental Design: Tobacco exposure was determined by plasma nicotine, cotinine, and smoking history. Precise mRNA expression was determined using our RNA-specific qRT-PCR strategy, and correlated with detailed demographic and clinical characteristics. Results: Several correlations of mRNA expression included (a) CYP1B1 in AC (positively with plasma nicotine level, P = 0.008; plasma cotinine level, P = 0.001), (b) GSTP1 in AC (positively with plasma cotinine level, P = 0.003), and (c) GSTP1 in BEC (negatively with smoke dose, P = 0.043; occupational risk, P = 0.019). CYP2A13 was rarely expressed in AC and not expressed in BEC. p16 expression was not correlated with any measured factor. For each gene, subjects showed expression that was individually concordant between these compartments. No clear association of mRNA expression with lung cancer risk was observed in this pilot analysis. Conclusions: The association between lung mRNA expression and tobacco exposure implies that gene-tobacco interaction is a measurable quantitative trait, albeit with wide interindividual variation. Gene expression tends to be concordant for alveolar and bronchial compartments for these genes in an individual, controlling for proximate tobacco exposure.

Original languageEnglish (US)
Pages (from-to)7562-7570
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number24
DOIs
StatePublished - Dec 15 2009

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Cotinine
Tobacco
Lasers
Smoking
Gene Expression
Lung
Messenger RNA
Nicotine
Genes
Lung Neoplasms
Tumor Suppressor Genes
Transcriptome
Smoke
Carcinogens
Cytochrome P-450 Enzyme System
Research Design
History
Demography
RNA
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Smoking-related gene expression in laser capture-microdissected human lung. / Tan, Xiang Lin; Wang, Tao; Xiong, Shengli; Kumar, Shalini V.; Han, Weiguo; Spivack, Simon D.

In: Clinical Cancer Research, Vol. 15, No. 24, 15.12.2009, p. 7562-7570.

Research output: Contribution to journalArticle

Tan, Xiang Lin ; Wang, Tao ; Xiong, Shengli ; Kumar, Shalini V. ; Han, Weiguo ; Spivack, Simon D. / Smoking-related gene expression in laser capture-microdissected human lung. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 24. pp. 7562-7570.
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AB - Purpose: Interindividual differences in quantitative expression could underlie a propensity for lung cancer. To determine precise individual gene expression signatures on a lung compartment-specific basis, we investigated the expression of carcinogen metabolism genes encoding cytochromes P450 (CYP) 1B1, 2A13, GSTP1, and a tumor suppressor gene p16 in laser capture-microdissected samples of human alveolar compartment (AC) and bronchial epithelial compartment (BEC) lung tissue from 62 smokers and nonsmokers. Experimental Design: Tobacco exposure was determined by plasma nicotine, cotinine, and smoking history. Precise mRNA expression was determined using our RNA-specific qRT-PCR strategy, and correlated with detailed demographic and clinical characteristics. Results: Several correlations of mRNA expression included (a) CYP1B1 in AC (positively with plasma nicotine level, P = 0.008; plasma cotinine level, P = 0.001), (b) GSTP1 in AC (positively with plasma cotinine level, P = 0.003), and (c) GSTP1 in BEC (negatively with smoke dose, P = 0.043; occupational risk, P = 0.019). CYP2A13 was rarely expressed in AC and not expressed in BEC. p16 expression was not correlated with any measured factor. For each gene, subjects showed expression that was individually concordant between these compartments. No clear association of mRNA expression with lung cancer risk was observed in this pilot analysis. Conclusions: The association between lung mRNA expression and tobacco exposure implies that gene-tobacco interaction is a measurable quantitative trait, albeit with wide interindividual variation. Gene expression tends to be concordant for alveolar and bronchial compartments for these genes in an individual, controlling for proximate tobacco exposure.

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