Abstract
Many epidemiological studies have explored the possible link between the susceptibility to alcohol related cancers, such as oesophageal cancers, and genetic variants of alcohol dehydrogenases (ADHs). Alcohol dehydrogenase class IV ADH7 is mainly expressed in the upper aero-digestive tract and is involved in the first pass ethanol metabolism. As far as we know, no study has described single nucleotide polymorphisms (SNPs) within ADH7 exons in the Caucasian population. Therefore, in a pilot study, we used the denaturing high performance liquid chromatography (DHPLC) method to screen 49 oesophageal cancer cases for SNPs in the ADH7 gene. A total of 5 SNPs was observed in this study: one SNP in the 5′ non-translated regions of exon 1, two SNPs in introns 3 and 4 and two others SNPs in exons 3 and 4. The SNP located in the exon 1, which has never been described before, occurred in a reverse TATA box whereas the SNP of exon 3 was a non-silent polymorphism. Because these two SNPs could potentially affect the transcription and/or the enzyme activity, their distribution was evaluated in a representative sample of healthy Caucasians (n=89) recruited in Lower Normandy. Frequencies of heterozygous samples ranged from 11% (exon 3) to 28% (exon 1). No homozygous samples were found. In this pilot study, the DHPLC method was suitable for both SNP screening and genotyping and allowed the detection of five SNPs in the ADH7 gene, two of which have never been described before, among the European population.
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Acknowledgements
The authors thank Dr P. Lebailly for purchasing DNA samples, G. Abéguillé and B. Moutinho for their technical assistance in DNA sequencing, G. Cadier for careful reading of the manuscript and the Gastroenterology Department of the University Hospital of Caen for purchasing blood samples. A. Abbas is a recipient of a fellowship from the Ligue Nationale Contre le Cancer, Comité de la Manche. Research was supported by grants from the Ligue Nationale Contre le Cancer, Comité de la Manche and Comité de l’Orne. DHPLC apparatus was bought with grants from Association pour la Recherche sur le Cancer (ARC) and the Contrat de Plan Etat-Région (Pôle de recherche en biologie médicale et épidémiologie de l’Université de Caen Basse-Normandie). Experiments described in this manuscript comply with the current French laws.
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Abbas, A., Lechevrel, M. & Sichel, F. Identification of new single nucleotid polymorphisms (SNP) in alcohol dehydrogenase class IV ADH7 gene within a French population. Arch Toxicol 80, 201–205 (2006). https://doi.org/10.1007/s00204-005-0031-7
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DOI: https://doi.org/10.1007/s00204-005-0031-7