title: N-Acetyltransferase (NAT) 2 acetylator status and age of tumour onset in patients with sporadic and familial, microsatellite stable (MSS) colorectal cancer.
abstract: BACKGROUND
  N-Acetyltransferase (NAT) 2 is an important enzyme involved in the metabolism of different xenobiotics, including potential carcinogens. Allelic variants of the NAT2 gene are determined by a pattern of single nucleotide polymorphisms (SNPs) resulting in slow (SA), intermediate (IA) or rapid acetylator (RA) phenotypes and causing the individual differences in the NAT2 metabolic capacity. To clarify the potential modifying role of the NAT2 acetylator status in microsatellite stable (MSS) colorectal cancer (CRC), we studied 140 patients with sporadic CRC (group 1) and 69 patients with CRC who met at least one criterion of the revised Bethesda guidelines (group 2).
  
  
  METHODS
  We did not observe any significant difference in the NAT2 acetylator status frequency between patients in both groups and 100 healthy controls (P=0.486). Regardless of a younger median age of tumour onset (AO) of 41 years in group 2 patients compared to 64 years in group 1 patients, no significant difference in AO was found between RA and SA status patients in both groups. The median AO in group 1 was 65 years in patients with RA and 63 years with SA status (P=0.065). The median AO in group 2 was 40 years in patients with RA and 42 years with SA status (P=0.814). Multivariate Cox regression analysis revealed that neither the NAT2 acetylator status (P=0.064 and 0.810, respectively) nor the gender (P=0.165 and 0.918, respectively) was a risk factor for the AO in both groups. These data do not support the hypothesis that the NAT2 acetylatorship acts as a modifying factor on the AO in sporadic and familial, microsatellite stable CRC.
authors.affiliation: Department of Visceral, Thoracic and Vascular Surgery, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, Germany. steffen.pistorius@uniklinikum-dresden.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Pistorius
authors.forename: Heike
authors.initials: H
authors.lastname: Goergens
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Jens
authors.initials: J
authors.lastname: Plaschke
authors.forename: Stefan
authors.initials: S
authors.lastname: Krueger
authors.forename: Ruth
authors.initials: R
authors.lastname: Hoehl
authors.forename: Hans-Detlev
authors.initials: HD
authors.lastname: Saeger
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
mesh_terms: D000107:Acetylation; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human