The relationship between genotype and chromosome aberration frequencies ina normal adult population

Cancer susceptibility differences may be attributed in part to genetic vari ation in genes involved in metabolism of environmental procarcinogens. Incr eased risks for some cancers have been linked to polymorphisms in certain p hase I and II genes, and have been associated with genomic instability and chromosomal aberrations, Aberration frequencies in general, and stable aber ration frequencies (translocations and insertions) in particular, are used as biomarkers for disease. Thus, knowledge of the genetic factors that infl uence the frequency of stable aberrations In a normal population is importa nt for cancer risk determination. In this work, genotypes for a number of x enobiotic enzymes (CYP1A1, CYP2D6, GSTM1, GSTT1, GSTP1, NAT1, NAT2 and epox ide hydrolase) and stable aberration frequencies were determined for 65 nor mal individuals aged 19-77 years. The population was divided at age 60 year s for analysis because there was a significant difference in stable aberrat ion frequencies between these groups. Subjects with low levels (0-66th perc entile) of stable aberrations were compared to those with high levels (67th percentile and above). Of all the genotypes studied, only NAT2 showed a no table difference between the high and the low stable aberration groups in t he percentage of polymorphisms observed, and this was seen only in the olde r subjects group. All individuals in the older-high stable aberration group were NAT2 rapid acetylator smokers. NAT2 slow acetylator smelters had sign ificantly lower stable aberration frequencies compared to the NAT2 rapid ac etylator smokers. Following previous work showing an increased risk of canc er associated with high levels of aberrations (above the 66th percentile), we hypothesize that smokers with the NAT2 rapid acetylator genotype may be at an increased risk for cancer. Pharmacogenetics 10:311-319 (C) 2000 Lippi ncott Williams & Wilkins.