N-Acetyltransferase polymorphisms and colorectal cancer: A HuGE review

N Brockton, J Little, L Sharp, S C Cotton

Research output: Contribution to journalLiterature review

129 Citations (Scopus)

Abstract

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-acetylation and are implicated in the activation and detoxification of known carcinogens. Single basepair substitutions in NAT2 tend to occur in combination with other substitutions within the gene, As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the 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 variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern, No consistent association has been found between acetylator phenotype or genotype and colorectal cancer, The lack of consistency can in part be accounted for by methodological factors, including limited statistical power, Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.

Original languageEnglish
Pages (from-to)846-861
Number of pages16
JournalAmerican Journal of Epidemiology
Volume151
Publication statusPublished - 2000

Keywords

  • colorectal neoplasms
  • epidemiology
  • genetics
  • N-acetyltransferase
  • NAT1
  • NAT2
  • N-ACETYLTRANSFERASE-2 GENETIC POLYMORPHISMS
  • AROMATIC AMINE ACETYLTRANSFERASE
  • RECURRENT SPONTANEOUS-ABORTION
  • SLOW ACETYLATOR MUTATIONS
  • DRUG-METABOLIZING-ENZYMES
  • SQUAMOUS-CELL CARCINOMA
  • COKE-OVEN WORKERS
  • BREAST-CANCER
  • CIGARETTE-SMOKING
  • NAT2 GENOTYPES

Cite this

N-Acetyltransferase polymorphisms and colorectal cancer: A HuGE review. / Brockton, N ; Little, J ; Sharp, L ; Cotton, S C .

In: American Journal of Epidemiology, Vol. 151, 2000, p. 846-861.

Research output: Contribution to journalLiterature review

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AU - Little, J

AU - Sharp, L

AU - Cotton, S C

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N2 - 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-acetylation and are implicated in the activation and detoxification of known carcinogens. Single basepair substitutions in NAT2 tend to occur in combination with other substitutions within the gene, As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the 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 variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern, No consistent association has been found between acetylator phenotype or genotype and colorectal cancer, The lack of consistency can in part be accounted for by methodological factors, including limited statistical power, Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.

AB - 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-acetylation and are implicated in the activation and detoxification of known carcinogens. Single basepair substitutions in NAT2 tend to occur in combination with other substitutions within the gene, As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the 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 variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern, No consistent association has been found between acetylator phenotype or genotype and colorectal cancer, The lack of consistency can in part be accounted for by methodological factors, including limited statistical power, Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.

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KW - RECURRENT SPONTANEOUS-ABORTION

KW - SLOW ACETYLATOR MUTATIONS

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KW - SQUAMOUS-CELL CARCINOMA

KW - COKE-OVEN WORKERS

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KW - CIGARETTE-SMOKING

KW - NAT2 GENOTYPES

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JO - American Journal of Epidemiology

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