Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders : a cross sectional study
- Author
- Hans B Ketelslegers, Roger WL Godschalk, Ralph WH Gottschalk, Ad M Knaapen, Gudrun Koppen, Greet Schoeters, Willy F Baeyens, Vera Nelen, Joep PM Geraedts, Joost HM van Delft, Jos CS Kleinjans and Nicolas Van Larebeke (UGent)
- Organization
- Abstract
- Background: We hypothesized that in Flanders (Belgium), the prevalence of at-risk genotypes for genotoxic effects decreases with age due to morbidity and mortality resulting from chronic diseases. Rather than polymorphisms in single genes, the interaction of multiple genetic polymorphisms in low penetrance genes involved in genotoxic effects might be of relevance. Methods: Genotyping was performed on 399 randomly selected adults (aged 50-65) and on 442 randomly selected adolescents. Based on their involvement in processes relevant to genotoxicity, 28 low penetrance polymorphisms affecting the phenotype in 19 genes were selected (xenobiotic metabolism, oxidative stress defense and DNA repair, respectively 13, 6 and 9 polymorphisms). Polymorphisms which, based on available literature, could not clearly be categorized a priori as leading to an 'increased risk' or a 'protective effect' were excluded. Results: The mean number of risk alleles for all investigated polymorphisms was found to be lower in the 'elderly' (17.0 +/- 2.9) than the 'adolescent' (17.6 +/- 3.1) subpopulation (P = 0.002). These results were not affected by gender nor smoking. The prevalence of a high (> 17 = median) number of risk alleles was less frequent in the 'elderly' (40.6%) than the 'adolescent' (51.4%) subpopulation (P = 0.002). In particular for phase II enzymes, the mean number of risk alleles was lower in the 'elderly' (4.3 +/- 1.6) than the 'adolescent' age group (4.8 +/- 1.9) P < 0.001 and the prevalence of a high (> 4 = median) number of risk alleles was less frequent in the 'elderly' (41.3%) than the adolescent subpopulation (56.3%, P < 0.001). The prevalence of a high (> 8 = median) number of risk alleles for DNA repair enzyme-coding genes was lower in the 'elderly' (37,3%) than the 'adolescent' subpopulation (45.6%, P = 0.017). Conclusions: These observations are consistent with the hypothesis that, in Flanders, the prevalence of at-risk alleles in genes involved in genotoxic effects decreases with age, suggesting that persons carrying a higher number of at risk alleles (especially in phase II xenobiotic-metabolizing or DNA repair genes) are at a higher risk of morbidity and mortality from chronic diseases. Our findings also suggest that, regarding risk of disease associated with low penetrance polymorphisms, multiple polymorphisms should be taken into account, rather than single ones.
- Keywords
- BLADDER-CANCER RISK, DRUG-METABOLIZING-ENZYMES, S-TRANSFERASE M1, LUNG-CANCER, GENETIC POLYMORPHISMS, HUMAN LONGEVITY, POOLED-ANALYSIS, MYOCARDIAL-INFARCTION, GSTT1 POLYMORPHISMS, OXIDATIVE STRESS
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-2308445
- MLA
- Ketelslegers, Hans B., et al. “Prevalence of At-Risk Genotypes for Genotoxic Effects Decreases with Age in a Randomly Selected Population in Flanders : A Cross Sectional Study.” ENVIRONMENTAL HEALTH, vol. 10, 2011, doi:10.1186/1476-069X-10-85.
- APA
- Ketelslegers, H. B., Godschalk, R. W., Gottschalk, R. W., Knaapen, A. M., Koppen, G., Schoeters, G., … Van Larebeke, N. (2011). Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders : a cross sectional study. ENVIRONMENTAL HEALTH, 10. https://doi.org/10.1186/1476-069X-10-85
- Chicago author-date
- Ketelslegers, Hans B, Roger WL Godschalk, Ralph WH Gottschalk, Ad M Knaapen, Gudrun Koppen, Greet Schoeters, Willy F Baeyens, et al. 2011. “Prevalence of At-Risk Genotypes for Genotoxic Effects Decreases with Age in a Randomly Selected Population in Flanders : A Cross Sectional Study.” ENVIRONMENTAL HEALTH 10. https://doi.org/10.1186/1476-069X-10-85.
- Chicago author-date (all authors)
- Ketelslegers, Hans B, Roger WL Godschalk, Ralph WH Gottschalk, Ad M Knaapen, Gudrun Koppen, Greet Schoeters, Willy F Baeyens, Vera Nelen, Joep PM Geraedts, Joost HM van Delft, Jos CS Kleinjans, and Nicolas Van Larebeke. 2011. “Prevalence of At-Risk Genotypes for Genotoxic Effects Decreases with Age in a Randomly Selected Population in Flanders : A Cross Sectional Study.” ENVIRONMENTAL HEALTH 10. doi:10.1186/1476-069X-10-85.
- Vancouver
- 1.Ketelslegers HB, Godschalk RW, Gottschalk RW, Knaapen AM, Koppen G, Schoeters G, et al. Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders : a cross sectional study. ENVIRONMENTAL HEALTH. 2011;10.
- IEEE
- [1]H. B. Ketelslegers et al., “Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders : a cross sectional study,” ENVIRONMENTAL HEALTH, vol. 10, 2011.
@article{2308445, abstract = {{Background: We hypothesized that in Flanders (Belgium), the prevalence of at-risk genotypes for genotoxic effects decreases with age due to morbidity and mortality resulting from chronic diseases. Rather than polymorphisms in single genes, the interaction of multiple genetic polymorphisms in low penetrance genes involved in genotoxic effects might be of relevance. Methods: Genotyping was performed on 399 randomly selected adults (aged 50-65) and on 442 randomly selected adolescents. Based on their involvement in processes relevant to genotoxicity, 28 low penetrance polymorphisms affecting the phenotype in 19 genes were selected (xenobiotic metabolism, oxidative stress defense and DNA repair, respectively 13, 6 and 9 polymorphisms). Polymorphisms which, based on available literature, could not clearly be categorized a priori as leading to an 'increased risk' or a 'protective effect' were excluded. Results: The mean number of risk alleles for all investigated polymorphisms was found to be lower in the 'elderly' (17.0 +/- 2.9) than the 'adolescent' (17.6 +/- 3.1) subpopulation (P = 0.002). These results were not affected by gender nor smoking. The prevalence of a high (> 17 = median) number of risk alleles was less frequent in the 'elderly' (40.6%) than the 'adolescent' (51.4%) subpopulation (P = 0.002). In particular for phase II enzymes, the mean number of risk alleles was lower in the 'elderly' (4.3 +/- 1.6) than the 'adolescent' age group (4.8 +/- 1.9) P < 0.001 and the prevalence of a high (> 4 = median) number of risk alleles was less frequent in the 'elderly' (41.3%) than the adolescent subpopulation (56.3%, P < 0.001). The prevalence of a high (> 8 = median) number of risk alleles for DNA repair enzyme-coding genes was lower in the 'elderly' (37,3%) than the 'adolescent' subpopulation (45.6%, P = 0.017). Conclusions: These observations are consistent with the hypothesis that, in Flanders, the prevalence of at-risk alleles in genes involved in genotoxic effects decreases with age, suggesting that persons carrying a higher number of at risk alleles (especially in phase II xenobiotic-metabolizing or DNA repair genes) are at a higher risk of morbidity and mortality from chronic diseases. Our findings also suggest that, regarding risk of disease associated with low penetrance polymorphisms, multiple polymorphisms should be taken into account, rather than single ones.}}, articleno = {{85}}, author = {{Ketelslegers, Hans B and Godschalk, Roger WL and Gottschalk, Ralph WH and Knaapen, Ad M and Koppen, Gudrun and Schoeters, Greet and Baeyens, Willy F and Nelen, Vera and Geraedts, Joep PM and van Delft, Joost HM and Kleinjans, Jos CS and Van Larebeke, Nicolas}}, issn = {{1476-069X}}, journal = {{ENVIRONMENTAL HEALTH}}, keywords = {{BLADDER-CANCER RISK,DRUG-METABOLIZING-ENZYMES,S-TRANSFERASE M1,LUNG-CANCER,GENETIC POLYMORPHISMS,HUMAN LONGEVITY,POOLED-ANALYSIS,MYOCARDIAL-INFARCTION,GSTT1 POLYMORPHISMS,OXIDATIVE STRESS}}, language = {{eng}}, pages = {{11}}, title = {{Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders : a cross sectional study}}, url = {{http://doi.org/10.1186/1476-069X-10-85}}, volume = {{10}}, year = {{2011}}, }
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