Arylamine N-acetyltransferase type 2 and glutathione S-transferases M1 and T1 polymorphisms in familial adenomatous polyposis.
Familial adenomatous polyposis (FAP) exhibits a variable phenotype even in carriers of the same adenomatous polyposis coli germline mutation. Xenobiotic-metabolizing enzymes such as N-acetyltransferases (NATs) and glutathione S-transferases (GSTs) were reported to modify the individual risk for colorectal cancer. We examined whether the polymorphisms of the NAT2, GSTM1, and GSTT1 enzymes affect age at diagnosis of first colorectal adenomas or extracolonic manifestations in 411 FAP patients. Neither age at diagnosis of colorectal adenomas nor occurrence of extra-intestinal tumors differed significantly between genotypes at the NAT2 and GSTM1 loci, whereas GSTT1 polymorphism showed an uncertain association with extra-intestinal manifestations. Combinations of supposed at risk genotypes of the three enzymes showed no significant differences either. Thus, NAT2, GSTM1, or GSTT1 are unlikely to modify the disease phenotype in FAP patients.
Lamberti
Christof
C
Institute of Human Genetics, University of Bonn, Bonn, Germany. c.lamberti@uni-bonn.de
Jungck
Matthias
M
Laarmann
Michael
M
Knapp
Michael
M
Caspari
Reiner
R
Friedl
Waltraut
W
Sauerbruch
Tilman
T
Propping
Peter
P
Kruse
Roland
R
D011125:Adenomatous Polyposis Coli / Q000201:enzymology / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality; D005838:Genotype; D018095:Germ-Line Mutation; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*
D025601:Adenomatous Polyposis Coli Protein; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1