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

The Ah receptor (AhR) is a ligand-dependent transcription factor that posit ively regulates the expression of the CYP1A1 gene. We investigated the gene tic polymorphisms of the AhR gene including the promoter, and examined the link between these polymorphisms, CYP1A1 inducibility and the lung cancer i ncidence. The AhR promoter region and the 11 exons of 30 subjects were scre ened. Among the three polymorphisms found, two [(2417)(A/G) ((157)G/A)] hav e never been described previously. The (1721)(G/A) and (2417)(A/G) are loca lized in exon 10 and lead to Arg(554)Lys and Met(786)Val substitutions, res pectively. The other polymorphism was found in the 5 ' -untransiated 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 stud ied. There is no significant association between (1721)(G/A), (157)(G/A) an d 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. (2 417)(A/G) was found in only one control of 100 (allele frequency 0.005). St atistical analysis did not show any relationship between both (1721)(G/A) a nd (157)(G/A) polymorphisms found and CYP1A1 inducibility. Considering the rareness of the (2417)(A/G) allelic variant we were not able to evaluate it s association with inducibility. In conclusion, none of the polymorphisms w ere found to play a key role in the CYP1A1 inducibility or in the susceptib ility to develop lung cancer.