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Carcinogenesis, Vol. 22, No. 11, 1819-1824, November 2001
© 2001 Oxford University Press


MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

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

Stéphane Cauchi, Isabelle Stücker1, Caroline Solas, Pierre Laurent-Puig, Sylvie Cénée1, Denis Hémon1, Michèle Jacquet2, Pierre Kremers2, Philippe Beaune,3 and Liliane Massaad-Massade

Laboratoire de Toxicologie Moléculaire, U-490 INSERM, 45 rue des Saints-Pères, F-75270 Paris Cedex, France,
1 Laboratoire de Recherches Epidémiologiques et Statistiques sur l'Environnement et la Santé, U-170 INSERM, Villejuif, France and
2 Laboratoire de Chimie Médicale, Sart Tilman, CHU, Liège, Belgique

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.


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