title: Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders: a cross sectional study.
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.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Hans B
authors.initials: HB
authors.lastname: Ketelslegers
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.forename: Ralph W H
authors.initials: RW
authors.lastname: Gottschalk
authors.forename: Ad M
authors.initials: AM
authors.lastname: Knaapen
authors.forename: Gudrun
authors.initials: G
authors.lastname: Koppen
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
authors.forename: Willy F
authors.initials: WF
authors.lastname: Baeyens
authors.forename: Vera
authors.initials: V
authors.lastname: Nelen
authors.forename: Joep P M
authors.initials: JP
authors.lastname: Geraedts
authors.forename: Joost H M
authors.initials: JH
authors.lastname: van Delft
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: van Larebeke
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000368:Aged; D000483:Alleles; D001530:Belgium / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019683:Penetrance; D011110:Polymorphism, Genetic; D015995:Prevalence; D018570:Risk Assessment; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*
chemical_list: D015262:Xenobiotics