Mahid Suhal S, Colliver Daniel W, Crawford Nigel P S, Martini Benjamin D, Doll Mark A, Hein David W, Cobbs Gary A, Petras Robert E, Galandiuk Susan
Price Institute of Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
BMC Med Genet. 2007 May 30;8:28. doi: 10.1186/1471-2350-8-28.
N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD.
A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs) were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM) method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes.
No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs.
This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.
N-乙酰基转移酶1（NAT1）和2（NAT2）是多态性同工酶，负责多种药物和致癌物的代谢。由NAT1和NAT2催化的乙酰化作用在芳胺代谢活化为引发致癌作用的亲电中间体过程中起重要作用。炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），二者均与结直肠癌（CRC）风险增加相关。我们推测NAT1和/或NAT2基因多态性导致了IBD中明显增加的癌症风险。
对729名白种人参与者进行了一项病例对照研究，其中包括123例CRC患者、201例CD患者、167例UC患者、15例IBD发育异常/癌症患者以及223名对照者。使用基于Taqman的技术进行NAT1和NAT2基因分型。对NAT1的8个单核苷酸多态性（SNP）和NAT2的7个SNP进行了特征分析。使用期望最大化（EM）方法估计单倍型频率。将疾病组分别与对照组比较每个个体SNP处的频率。对相同的组比较NAT1和NAT2单倍型的频率以及推导的NAT2表型。
任何比较均未发现统计学上的显著差异。NAT1 SNP和NAT2 SNP之间均存在强连锁不平衡。
本研究未证明NAT1和NAT2基因多态性与IBD或散发性CRC之间存在关联，尽管功效计算表明本研究有足够的样本量来检测频率差异小至0.05至0.15（取决于SNP或单倍型）。
