A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma

Robert J. Boissy, Mary A. Watson, David M. Umbach, Mark Deakin, James Elder, Richard C. Strange, Douglas A. Bell

Research output: Contribution to journalArticle

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Abstract

In humans, aromatic and heterocyclic amine carcinogens may be acetylated by the expression products of either of the N-acetyltransferase genes, NAT1 or NAT2. This conjugation reaction can result in either activation or detoxication of these carcinogens depending on the tissue involved. Recent studies suggest that polymorphisms in NAT1 or NAT2 may modulate cancer risk. To determine if genetic differences in NAT1 and NAT2 could alter risk of gastric cancer, we tested for the presence of polymorphic N-acetyltransferase alleles (both NAT1 and NAT2) in a preliminary study of 94 gastric adenocarcinoma patients and 112 control subjects from North Staffordshire, England. We used established PCR protocols to genotype for NAT2 and NAT1 alleles (NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14; NAT1*3, NAT1*4, NAT1*10, and NAT1*11), and implemented an oligonucleotide ligation assay (OLA) to test for low-activity NAT1 alleles [NAT1*14 (G560A), NAT1*15 (C559T), and NAT1*17 (C190T)]. No significant increased risk was observed for NAT2 acetylation genotypes. However, among all cases, we found that individuals inheriting a variant NAT1 allele, NAT1*10, have a significantly elevated risk for gastric cancer (OR = 2.2, 95% CI 1.2-3.9, P < 0.01). Interestingly, the risk observed for NAT1*10 appears to be solely associated with advanced-stage tumors (OR = 4.8, P < 0.001), suggesting a possible role in progression to advanced disease. This preliminary finding needs confirmation in a larger, detailed epidemiological study.

Original languageEnglish (US)
Pages (from-to)507-511
Number of pages5
JournalInternational Journal of Cancer
Volume87
Issue number4
DOIs
StatePublished - Sep 2 2000

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Stomach
Adenocarcinoma
Alleles
Acetyltransferases
Carcinogens
Stomach Neoplasms
Genotype
Acetylation
Oligonucleotides
England
Amines
Ligation
Epidemiologic Studies
Neoplasms
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma. / Boissy, Robert J.; Watson, Mary A.; Umbach, David M.; Deakin, Mark; Elder, James; Strange, Richard C.; Bell, Douglas A.

In: International Journal of Cancer, Vol. 87, No. 4, 02.09.2000, p. 507-511.

Research output: Contribution to journalArticle

Boissy, Robert J. ; Watson, Mary A. ; Umbach, David M. ; Deakin, Mark ; Elder, James ; Strange, Richard C. ; Bell, Douglas A. / A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma. In: International Journal of Cancer. 2000 ; Vol. 87, No. 4. pp. 507-511.
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