N-acetyl transferase 1: two polymorphisms in coding sequence identified in colorectal cancer patients

British Journal of Cancer
A L HubbardD J Harrison

Abstract

Increased cancer risk has been associated with functional polymorphisms that occur within the genes coding for the N-acetyltransferase enzymes NAT1 and NAT2. We detected two NAT1 polymorphisms in colorectal cancer patients by heteroduplex analysis. DNA sequencing revealed the wild-type sequence (NAT1*4) and two single base substitutions at adjacent positions 999 bp (C to T, NAT1*14) and 1000 bp (G to A, NAT1*15) of the gene, changing Arg187 to a stop codon and Arg187 to Gln respectively. NAT1 alleles NAT1*4 (0.98) and NAT1*15 (0.02) were present at a similar frequency in patients with colorectal cancer (n=260) and in a Scottish control group (n=323). The third allele, NAT1*14, was present only in the colorectal cancer group at a frequency of 0.006. NAT1 genotype NAT1*4/ NAT1*15 was significantly less frequent in individuals that had a slow NAT2 genotype. This was observed in both cancer and control groups and suggests that this association was unrelated to cancer risk. We conclude that polymorphisms within the coding region of the NAT1 gene are infrequent and do not appear to have an independent association with colorectal cancer risk. However, the relationship between NAT1 and NAT2 polymorphisms appears non-random, suggesting ...Continue Reading

Citations

Apr 23, 2002·Pharmacogenomics·Frédérique PompeoEdith Sim
Mar 19, 2014·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Hassan R Dhaini, Loulou Kobeissi
Mar 5, 2002·Pharmacogenetics·Naoko IshibeNathaniel Rothman
Nov 1, 2005·Drug Metabolism Reviews·Sotiria Boukouvala, Giannoulis Fakis
Jun 24, 2008·Journal of Toxicology and Environmental Health. Part a·Hermann C RoemerKlaus Golka
Jan 1, 2000·Environmental Health and Preventive Medicine·X YangK Morimoto
Nov 6, 2003·International Journal of Cancer. Journal International Du Cancer·Cinzia MagagnottiLuisa Airoldi
Mar 10, 2001·Trends in Pharmacological Sciences·A UptonE Sim
Feb 22, 2003·Toxicology Letters·Kent R Mitchell, David Warshawsky

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