LB-130

It is suggested that certain individuals are at higher risk for developing cancer compared to other members of the population due to genetic polymorphisms in genes involved in the biotransformation of environmental carcinogens. Numerous studies have focused on genetic polymorphisms in genes coding for phase I and II enzymes, such as cytochrome P450s (CYP450), Glutathione-S-transferases (GSTs) and N-acetyltransferases (NATs) in relation to several types of cancers after exposure to environmental genotoxins. Assuming that an unfavorable combination of environmental exposures and an at risk genotype is indeed associated with disease development, it can be postulated that the presence of risk alleles in a healthy population will be lower in a randomly selected group of healthy old individuals as compared to young individuals. In the current study, 439 adolescents (average age: 15 years) and 367 adults (average age: 60 years) originating from the same region in Belgium, were genotyped for 18 polymorphisms in 11 genes involved in biotransformation of environmental carcinogens. Genotypes were coded based on their putative risk for cancer development, and subsequently, a sum of risk alleles was computed for each individual. Comparison of this sum of risk alleles between the two populations indeed showed that the presence of a relatively high number of risk alleles was less frequent in the adult population (40% of the individuals with >7 risk alleles) compared to the adolescent population (61% of subjects carried >7 risk alleles, P=0.001). To further investigate which biotransformation processes contribute most to this effect, a separate sum of risk alleles for both phase I as well as phase II related genes was computed. The sum of risk alleles in phase I genes (CYP450’s) did not differ between the ‘old’ and ‘young’ study population. However, a high sum of risk alleles for phase II enzymes (GSTs, NATs; >5 risk alleles) was significantly less frequent in adults (40%) compared to the adolescent population (56%, P=0.000). It is concluded that in a healthy population, the number of at-risk alleles of genes involved in the biotransformation of carcinogenic compounds is lower in an random selection of ‘old’ individuals compared to ‘young’ individuals, which further supports the hypothesis that an at risk genotype may modify the risk for environmental cancer development.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA