Carcinogenesis, Vol 19, 37-41, Copyright © 1998 by Oxford University Press
JP Gil and MC Lechner
Here we report that colorectal cancer patients show a markedly higher
frequency (3-fold) of wild-type NAT2*4 allele homozygotes than the control
population. However, a marked difference in NAT2*4/NAT2*4 genotype
frequency associated with the patients gender was observed pointing to a
male-specific effect of this genotype as a risk factor in colon cancer. The
arylamine-N-acetyltransferase (E.C. 2.3.1.5.) NAT2, a phase II
detoxification enzyme, has been implicated in procarcinogen activation,
namely from food contained arylamines, cigarette smoking, as well as
environmental amines of various types. NAT2 is encoded by a polymorphic
gene presenting several allelic variants encoding partially inactive
enzymes expressed in human liver and colon. Epidemiological studies based
on phenotype determination have long indicated the importance of the NAT2
active phenotype as a susceptibility factor in colorectal cancer. In the
present study we investigated the NAT2 allelic frequencies and genotype
distribution in a group of 114 unrelated colorectal cancer patients, in
parallel with 201 healthy Portuguese subjects. We first demonstrate that
the frequency of the wild-type NAT2*4 allele in the Portuguese sample
population (23.4%) does not significantly differ from the values described
for other Europeans. Besides the 3-fold higher frequency of NAT2*4
homozygotes found in colorectal cancer subjects, the NAT2*4/NAT2*5A
compound genotype, known to determine a faster acetylator phenotype than
other heterozygotic combinations, also increased by the same order of
magnitude. These two genotypes represent 32% of the patients population
versus 11% of the healthy controls. Taken together, our results strongly
indicate that NAT2 genotype, particularly NAT2*4 allele zygosity,
constitutes an individual susceptibility trait associated with sporadic
colorectal cancer development, probably due to the local dietary habits in
Portugal.
ARTICLES
Increased frequency of wild-type arylamine-N-acetyltransferase allele NAT2*4 homozygotes in Portuguese patients with colorectal cancer
Gulbenkian Institute of Sciences, Oeiras and Molecular Biology Unit, Faculty of Pharmacy, University of Lisbon, Lisboa, Portugal.
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