University of Louisville
N-acetyltransferase-1 and -2 SNP Data into Genotype and Phenotype: Applications to Cancer Risk Assessment
Institution
University of Louisville
Faculty Advisor/ Mentor
David W. Hein; Mark A. Doll
Abstract
Many carcinogenic chemicals may require activation and inactivation by enzymes. Genetic polymorphisms in these enzymes may infer genetic predisposition to cancer following exposure to environmental factors. N-acetyltransferase-1 (NAT1) and -2 (NAT2) are important enzymes in the metabolism of aromatic amines. NAT1 and NAT2 exhibit genetic polymorphism (over 25 human alleles for both NAT1 and NAT2 have been identified) in human populations primarily due to presence of single nucleotide polymorphisms (SNPs). New high throughput methods to assess the presence of these SNPs in the human NAT1 and NAT2 genes have been developed recently and have facilitated much larger molecular epidemiological studies to assess the role of NAT1 and/or NAT2 phenotype on cancer risk following exposure to environmental factors. However, interpretation of the large data sets generated through these high throughput methods has been hindered by genotype misclassifications and human errors inherent in manually translating SNP data to genotype and phenotype in large data sets. For example, there are over 6500 and 2100 possibilities for NAT1 and NAT2, respectively. To resolve this problem, Microsoft Visual Basic for Applications was used to develop a computer program that processes SNP data directly from Microsoft Excel. The program easily and rapidly converts the NAT1 and NAT2 SNP data into alleles, genotypes, and phenotypes and is quite useful in assessing the modifying effects of NAT1 and/or NAT2 genotype on cancer risk. The new program results in substantial decreases in time and human error.
N-acetyltransferase-1 and -2 SNP Data into Genotype and Phenotype: Applications to Cancer Risk Assessment
Many carcinogenic chemicals may require activation and inactivation by enzymes. Genetic polymorphisms in these enzymes may infer genetic predisposition to cancer following exposure to environmental factors. N-acetyltransferase-1 (NAT1) and -2 (NAT2) are important enzymes in the metabolism of aromatic amines. NAT1 and NAT2 exhibit genetic polymorphism (over 25 human alleles for both NAT1 and NAT2 have been identified) in human populations primarily due to presence of single nucleotide polymorphisms (SNPs). New high throughput methods to assess the presence of these SNPs in the human NAT1 and NAT2 genes have been developed recently and have facilitated much larger molecular epidemiological studies to assess the role of NAT1 and/or NAT2 phenotype on cancer risk following exposure to environmental factors. However, interpretation of the large data sets generated through these high throughput methods has been hindered by genotype misclassifications and human errors inherent in manually translating SNP data to genotype and phenotype in large data sets. For example, there are over 6500 and 2100 possibilities for NAT1 and NAT2, respectively. To resolve this problem, Microsoft Visual Basic for Applications was used to develop a computer program that processes SNP data directly from Microsoft Excel. The program easily and rapidly converts the NAT1 and NAT2 SNP data into alleles, genotypes, and phenotypes and is quite useful in assessing the modifying effects of NAT1 and/or NAT2 genotype on cancer risk. The new program results in substantial decreases in time and human error.