Exon 5 Polymorphisms in the O 6-Alkylguanine DNA Alkyltransferase Gene and Lung Cancer Risk in Non–Smokers Exposed to Second-Hand Smoke
| Autor: | Irene Brüske-Hohlfeld, Catherine Cohet, Paul Brennan, Fredrik Nyberg, Anush Mukeria, Stephane Borel, Janet E. Hall, Vali Constantinescu, Simone Benhamou, Paolo Boffetta |
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| Přispěvatelé: | Cohet, C., Borel, S., Nyberg, F., Mukeria, A., Brüske-Hohlfeld, I., Constantinescu, V., Benhamou, S., Brennan, P., Hall, J., Boffetta, P. |
| Rok vydání: | 2004 |
| Předmět: |
Male
Lung Neoplasms Genotype Epidemiology Population Adenocarcinoma Biology Polymerase Chain Reaction Risk Assessment Small-cell carcinoma O(6)-Methylguanine-DNA Methyltransferase Exon Carcinoma Non-Small-Cell Lung medicine Humans Genetic Predisposition to Disease Allele Lung cancer education Allele frequency Alleles Aged Genetics education.field_of_study Polymorphism Genetic Exons Sequence Analysis DNA Middle Aged medicine.disease Lung cancer susceptibility Diet Oncology Case-Control Studies Carcinoma Squamous Cell Cancer research Population study Female Tobacco Smoke Pollution |
| Zdroj: | Cancer Epidemiol. Biomarkers Prev. 13, 320-323 (2004) |
| ISSN: | 1538-7755 1055-9965 |
| DOI: | 10.1158/1055-9965.epi-03-0120 |
| Popis: | Purpose: The objective of the study was to examine the association of three exon 5 variants in the O6-alkylguanine DNA alkyltransferase (AGT) gene involved in the repair of the mutagenic DNA lesion O6-alkylguanine formed by nitrosamines, with lung cancer risk in never-smokers. Experimental Design: Exon 5 of the AGT gene was sequenced in genomic DNA from 136 cases and 133 hospital- or population-based controls for whom questionnaire information on second-hand smoke and diet was available to determine the frequencies of the Gly160Arg, Ile143Val, and Lys178Arg variant alleles. Results: No codon 160Arg variant alleles were found in the study population. The codon 143Val and 178Arg variant alleles, present at allele frequencies of 0.07, showed 100% linkage. The odds ratio (OR) of lung cancer for these variant carriers was 2.05 [95% confidence interval (CI) 1.03–4.07]. The risk varied between the different lung cancer pathologies with an increased risk for adenocarcinoma (OR 2.67, 95% CI 1.21–5.87) or small cell carcinoma (OR 4.83, 95% CI 0.91–25.7) but not for squamous cell carcinoma (OR 1.07, 95% CI 0.27–4.18). Compared with individuals carrying the mutant alleles unexposed to second-hand smoke, the OR for exposed variant carriers was 1.95 (95% CI 0.53–1.15); a similar interaction, although not significative, was observed for low consumption of cruciferous vegetables and for green vegetables and tomatoes. Conclusions: These results point toward a role of AGT polymorphisms in lung cancer susceptibility among never-smokers, in particular among subjects exposed to environmental carcinogens. |
| Databáze: | OpenAIRE |
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