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A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma
Author(s) -
Boissy Robert J.,
Watson Mary A.,
Umbach David M.,
Deakin Mark,
Elder James,
Strange Richard C.,
Bell Douglas A.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000815)87:4<507::aid-ijc7>3.0.co;2-i
Subject(s) - genotype , heterocyclic amine , arylamine n acetyltransferase , n acetyltransferase , cancer , allele , carcinogen , adenocarcinoma , biology , genetics , microbiology and biotechnology , medicine , gene , acetylation
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. Int. J. Cancer 87:507–511, 2000. © 2000 Wiley‐Liss, Inc.