This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frazier, M. L. Articles by Amos, C. I. Search for Related Content PubMed PubMed Citation Articles by Frazier, M. L. Articles by Amos, C. I.

Age-associated Risk of Cancer among Individuals with N-Acetyltransferase 2 (NAT2) Mutations and Mutations in DNA Mismatch Repair Genes¹

Departments of Epidemiology [M. L. F., F. T. O., S. K., X. G., I. C., C. I. A.], Pathology [R. L.], and Gastrointestinal Medical Oncology and Digestive Diseases [P. M. L.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

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.

This article has been cited by other articles:

				M. Pande, C. I. Amos, D. R. Osterwisch, J. Chen, P. M. Lynch, R. Broaddus, and M. L. Frazier Genetic Variation in Genes for the Xenobiotic-Metabolizing Enzymes CYP1A1, EPHX1, GSTM1, GSTT1, and GSTP1 and Susceptibility to Colorectal Cancer in Lynch Syndrome Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2393 - 2401. [Abstract] [Full Text] [PDF]

				M. Pande, J. Chen, C. I. Amos, P. M. Lynch, R. Broaddus, and M. L. Frazier Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1753 - 1759. [Abstract] [Full Text] [PDF]

				P. T. Campbell, L. Edwards, J. R. McLaughlin, J. Green, H. B. Younghusband, and M. O. Woods Cytochrome P450 17A1 and Catechol O-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland Clin. Cancer Res., July 1, 2007; 13(13): 3783 - 3788. [Abstract] [Full Text] [PDF]

				B. A. Talseth, C. Meldrum, J. Suchy, G. Kurzawski, J. Lubinski, and R. J. Scott Genetic Polymorphisms in Xenobiotic Clearance Genes and Their Influence on Disease Expression in Hereditary Nonpolyposis Colorectal Cancer Patients. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2307 - 2310. [Abstract] [Full Text] [PDF]

				J. S. Jones, C. I. Amos, M. Pande, X. Gu, J. Chen, I. M. Campos, Q. Wei, M. Rodriguez-Bigas, P. M. Lynch, and M. L. Frazier DNMT3b Polymorphism and Hereditary Nonpolyposis Colorectal Cancer Age of Onset. Cancer Epidemiol. Biomarkers Prev., May 1, 2006; 15(5): 886 - 891. [Abstract] [Full Text] [PDF]

				M. Zecevic, C. I. Amos, X. Gu, I. M. Campos, J. S. Jones, P. M. Lynch, M. A. Rodriguez-Bigas, and M. L. Frazier IGF1 Gene Polymorphism and Risk for Hereditary Nonpolyposis Colorectal Cancer J Natl Cancer Inst, January 18, 2006; 98(2): 139 - 143. [Abstract] [Full Text] [PDF]

				W M Grady Molecular basis for subdividing hereditary colon cancer? Gut, December 1, 2005; 54(12): 1676 - 1678. [Full Text] [PDF]

				S Kruger, A Bier, C Engel, E Mangold, C Pagenstecher, M von Knebel Doeberitz, E Holinski-Feder, G Moeslein, K Schulmann, J Plaschke, et al. The p53 codon 72 variation is associated with the age of onset of hereditary non-polyposis colorectal cancer (HNPCC) J. Med. Genet., October 1, 2005; 42(10): 769 - 773. [Abstract] [Full Text] [PDF]

				K. Sotamaa, S. Liyanarachchi, J.-P. Mecklin, H. Jarvinen, L. A. Aaltonen, P. Peltomaki, and A. de la Chapelle p53 Codon 72 and MDM2 SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome Clin. Cancer Res., October 1, 2005; 11(19): 6840 - 6844. [Abstract] [Full Text] [PDF]

				J. Shawn Jones, X. Gu, I. M. Campos, P. M. Lynch, C. I. Amos, and M. L. Frazier GSTM1 Polymorphism Does Not Affect Hereditary Nonpolyposis Colorectal Cancer Age of Onset Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 676 - 678. [Full Text] [PDF]

				M D Crabtree, C Fletcher, M Churchman, S V Hodgson, K Neale, R K S Phillips, and I P M Tomlinson Analysis of candidate modifier loci for the severity of colonic familial adenomatous polyposis, with evidence for the importance of the N-acetyl transferases Gut, February 1, 2004; 53(2): 271 - 276. [Abstract] [Full Text] [PDF]

				G E Goodman Lung cancer * 1: Prevention of lung cancer Thorax, November 1, 2002; 57(11): 994 - 999. [Abstract] [Full Text] [PDF]

				S. Bala and P. Peltomaki CYCLIN D1 as a Genetic Modifier in Hereditary Nonpolyposis Colorectal Cancer Cancer Res., August 1, 2001; 61(16): 6042 - 6045. [Abstract] [Full Text] [PDF]