N-Acetyltransferase polymorphisms and colorectal cancer: A HuGE review

The two expressed genes coding for N-acetyltransferase (NAT) activity, NAT1 and NAT2, are located on chromosome 8 at 8p21.3-23.1 and are polymorphic, Both enzymes are capable of N-acetylation, O-acetylation, and N,O-acetylati on and are implicated in the activation and detoxification of known carcino gens. Single basepair substitutions in NAT2 tend to occur in combination wi th other substitutions within the gene, As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of th e reported polymorphisms exist, It is important to select a method that is appropriate to the population being studied. The functional significance of many NAT allelic variants has not been determined. Geographic and ethnic v ariation in the frequency of NAT2 genotypes associated with fast or interme diate acetylation has been observed. Insufficient data for NAT1 genotypes a re available to reveal a clear geographic pattern, No consistent associatio n has been found between acetylator phenotype or genotype and colorectal ca ncer, The lack of consistency can in part be accounted for by methodologica l factors, including limited statistical power, Possible interactions betwe en the NAT genes and either environmental exposures or other polymorphic ge nes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical pow er to detect interactions.