Polymorphisms of human aryl hydrocarbon receptor (AhR) gene in a French population: relationship with CYP1A1 inducibility and lung cancer

• Published in: Carcinogenesis (New York) Vol. 22; no. 11; pp. 1819 - 1824
• Main Authors: Cauchi, Stéphane, Stücker, Isabelle, Solas, Caroline, Laurent-Puig, Pierre, Cénée, Sylvie, Hémon, Denis, Jacquet, Michèle, Kremers, Pierre, Beaune, Philippe, Massaad-Massade, Liliane
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2001; Oxford Publishing Limited (England)
• Subjects: Adenocarcinoma - enzymology; Adenocarcinoma - genetics; AHH; AhR; AhR gene; aryl hydrocarbon hydroxylase; aryl hydrocarbon receptor; B[a]P; benzo[a]pyrene; Biological and medical sciences; Carcinoma, Small Cell - enzymology; Carcinoma, Small Cell - genetics; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - genetics; Case-Control Studies; CYP; CYP1A1 gene; cytochrome P-450; Cytochrome P-450 CYP1A1 - biosynthesis; denaturing gradient gel electrophoresis; DGGE; DNA Primers; Electrophoresis; Enzyme Induction; Exons; France; Genetic Predisposition to Disease; Genotype; Humans; Ligases - metabolism; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Medical sciences; Middle Aged; OLA; oligonucleotide ligation assay; Oligonucleotides - chemistry; PAH; Pneumology; polycyclic aromatic hydrocarbons; Polymerase Chain Reaction; Polymorphism, Genetic; Promoter Regions, Genetic; Receptors, Aryl Hydrocarbon - genetics; Sequence Analysis, DNA; Tumors of the respiratory system and mediastinum; xenobiotic responsive element; XRE; France; Europe; Human; Lung disease; Respiratory disease; Enzyme; Isozyme; Gene product; Cytochrome P450; Genetic variant; Genotype; Case control study; Malignant tumor; Gene expression; Carcinogenesis; Bronchopulmonary; Ah receptor; Allele; Risk factor; Predisposition; Bronchus disease; Drug-metabolizing enzyme; Genetics; Transcription factor; Polymorphism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/22.11.1819

The Ah receptor (AhR) is a ligand-dependent transcription factor that positively regulates the expression of the CYP1A1 gene. We investigated the genetic polymorphisms of the AhR gene including the promoter, and examined the link between these polymorphisms, CYP1A1 inducibility and the lung cancer incidence. The AhR promoter region and the 11 exons of 30 subjects were screened. Among the three polymorphisms found, two [2417(A/G) (157G/A)] have never been described previously. The 1721(G/A) and 2417(A/G) are localized in exon 10 and lead to Arg554Lys and Met786Val substitutions, respectively. The other polymorphism was found in the 5′-untranslated region, resulting in the substitution of a G by an A at position 157 157(G/A). To evaluate the frequency of this allelic variant found, a DNA library of a case-control study of lung cancer (162 controls and 177 patients) was studied. There is no significant association between 1721(G/A), 157(G/A) and lung cancer: 1721(G/A) and 157(G/A) were detected at the same allele frequency of 0.086 and 0.25, respectively in both controls and patients. 2417(A/G) was found in only one control of 100 (allele frequency 0.005). Statistical analysis did not show any relationship between both 1721(G/A) and 157(G/A) polymorphisms found and CYP1A1 inducibility. Considering the rareness of the 2417(A/G) allelic variant we were not able to evaluate its association with inducibility. In conclusion, none of the polymorphisms were found to play a key role in the CYP1A1 inducibility or in the susceptibility to develop lung cancer.