RT Journal Article
SR Electronic
T1 Age-associated Risk of Cancer among Individuals with <em>N</em>-Acetyltransferase 2 (<em>NAT2</em>) Mutations and Mutations in DNA Mismatch Repair Genes
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 1269
OP 1271
VO 61
IS 4
A1 Frazier, Marsha L.
A1 O’Donnell, Frederick T.
A1 Kong, Shouming
A1 Gu, Xiangjun
A1 Campos, Imelda
A1 Luthra, Rajyalakshmi
A1 Lynch, Patrick M.
A1 Amos, Christopher I.
YR 2001
UL http://cancerres.aacrjournals.org/content/61/4/1269.abstract
AB Mutations in N-acetyltransferase 2 (NAT2), a highly polymorphic enzyme involved in the metabolism of xenobiotics and carcinogens, may affect risk for colorectal cancer (CRC), especially among individuals with germ-line mutations in DNA mismatch repair genes. We determined the NAT2 genotypes and allele frequencies for 86 individuals with CRC who had mutations in hMLH1, hMSH2, or hPMS1. No significant difference in time to onset was observed between rapid (NAT2*4) and slow (NAT2*5, NAT2*6, and NAT2*7) acetylators. However, when individuals were stratified separately by NAT2 polymorphism (NAT2*5, NAT2*6, and NAT2*7), those who were heterozygous at the mutant locus NAT2*7 after adjustment for the NAT2 mutant loci NAT2*5 and NAT2*6 had a significantly higher risk of CRC (hazard ratio, 2.96; P = 0.012) and all of the cancers (hazard ratio, 3.37; P = 0.00004) than individuals homozygous for wild type at the NAT2*7 allele. These findings suggest that NAT2 genotype may be an important factor in tumorigenesis of CRC and cancers related to hereditary nonpolyposis CRC among individuals with mismatch repair defects. ©2001 American Association for Cancer Research.