N-acetyltransferase 2 genotype in colorectal cancer and selective gene retention in cancers with chromosome 8p deletions.
BACKGROUND
Genetic polymorphisms in N-acetyltransferase (NAT2) can change the normally fast acetylation of substrates to slow acetylation, and have been associated with the development of some cancers. The NAT2 locus may also suffer dysregulation during cancer progression, as the gene resides on chromosome 8p22, a region which is frequently deleted in colorectal cancer.


METHODS
A polymerase chain reaction based method was used to determine NAT2 genotype in 275 patients with colon cancer and 343 normal control DNAs. Within the cancer group, 65 cases known to contain deletions in chromosome 8p were examined for loss of heterozygosity at the NAT2 locus.


RESULTS
Overall, there was no statistical difference in frequency or distribution of NAT2 alleles and genotype between colon cancer and control groups. There was a significant association between the slow acetylation genotype and early age of onset. NAT2 genotype did not vary with other clinical features of colon cancer, which included Dukes's stage, site of tumour, and sex. Of 48 informative cases, only three (6%) showed loss of heterozygosity, indicating that the NAT2 locus is not commonly deleted in colorectal cancer. This suggests that NAT2 is retained during the process of allele loss possibly because of its proximity to a gene necessary for cell viability.


CONCLUSIONS
NAT2 does not play a major role in colorectal cancer risk, but may influence risk in some age groups. The nature of the loss of heterozygosity at the chromosome 8p site is complex and is worthy of further study.
Hubbard
A L
AL
Sir Alastair Currie CRC Laboratories, University of Edinburgh.
Harrison
D J
DJ
Moyes
C
C
Wyllie
A H
AH
Cunningham
C
C
Mannion
E
E
Smith
C A
CA
D000107:Acetylation; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D005819:Genetic Markers; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human