Pistorius Steffen, Goergens Heike, Engel Christoph, Plaschke Jens, Krueger Stefan, Hoehl Ruth, Saeger Hans-Detlev, Schackert Hans K
Department of Visceral, Thoracic and Vascular Surgery, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Int J Colorectal Dis. 2007 Feb;22(2):137-43. doi: 10.1007/s00384-006-0171-0. Epub 2006 Aug 2.
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).
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.
N - 乙酰转移酶（NAT）2是一种重要的酶，参与包括潜在致癌物在内的多种外源性物质的代谢。NAT2基因的等位基因变异由单核苷酸多态性（SNP）模式决定，导致慢乙酰化（SA）、中间乙酰化（IA）或快乙酰化（RA）表型，并造成NAT2代谢能力的个体差异。为阐明NAT2乙酰化状态在微卫星稳定（MSS）结直肠癌（CRC）中的潜在调节作用，我们研究了140例散发性CRC患者（第1组）和69例符合修订的贝塞斯达指南至少一项标准的CRC患者（第2组）。
我们未观察到两组患者与100名健康对照者之间NAT2乙酰化状态频率有任何显著差异（P = 0.486）。尽管第2组患者肿瘤发病（AO）的中位年龄为41岁，比第1组患者的64岁年轻，但两组中RA和SA状态患者的AO无显著差异。第1组中，RA状态患者的AO中位年龄为65岁，SA状态患者为63岁（P = 0.065）。第2组中，RA状态患者的AO中位年龄为40岁，SA状态患者为42岁（P = 0.814）。多变量Cox回归分析显示，NAT2乙酰化状态（分别为P = 0.064和0.810）和性别（分别为P = 0.165和0.918）均不是两组中AO的危险因素。这些数据不支持NAT2乙酰化状态在散发性和家族性微卫星稳定CRC中作为AO调节因子的假说。
