Cascorbi I, Brockmöller J, Mrozikiewicz P M, Bauer S, Loddenkemper R, Roots I
Institute of Clinical Pharmacology, University Clinic Charité, Humboldt University of Berlin, Germany.
Cancer Res. 1996 Sep 1;56(17):3961-6.
The polymorphic arylamine N-acetyltransferase (NAT2) is supposed to be a susceptibility factor for certain malignancies. A phenotyping study in 389 lung cancer patients revealed a similar distribution of rapid and slow acetylators by the caffeine test to that in 657 reference subjects (odds ratio, 1.05; 95% confidence limits, 0.81, 1.36; not significant). A separate group of 155 lung cancer patients was studied by genotyping NAT2 and was compared with a matched reference group of 310 unrelated patients and with 278 healthy volunteers. The NAT2 genotype was characterized by PCR-RFLP at nucleotide positions 191, 282, 341, 481, 590, 803, and 857. For evaluation of nucleotide 341, a 3'-mismatch primer was used. Homozygous wild-type genotypes NAT24/4 were confirmed by DNA sequencing. Genotypes for rapid acetylation amounted to 43.9% among lung cancer and 41.6% among reference patients (odds ratio, 1.10 95% confidence limits, 0.73, 1.65; not significant). Discrimination into homozygous and heterozygous carriers of allele NAT24 revealed a distinct over-representation of NAT24/4 genotypes amid lung cancer patients (odds ratio, 2.36; 95% confidence limits, 1.05, 5.32; P = 0.018). Logistic regression analysis considering sex, age, and smoking provided an odds ratio of 3.04 (95% confidence limits, 1.37, 6.75; P = 0.003). Hence, carriers of the NAT24/*4 genotype, with its especially high acetylation capacity, are at significantly increased risk to lung cancer.
多态性芳胺N - 乙酰基转移酶（NAT2）被认为是某些恶性肿瘤的易感性因素。一项对389名肺癌患者的表型研究显示，通过咖啡因试验得出的快速和慢速乙酰化者的分布与657名对照受试者相似（优势比为1.05；95%置信区间为0.81至1.36；无显著性差异）。对另一组155名肺癌患者进行了NAT2基因分型研究，并与310名不相关的对照患者以及278名健康志愿者组成的匹配对照组进行比较。NAT2基因型通过对核苷酸位置191、282、341、481、590、803和857进行PCR - RFLP分析来确定。对于核苷酸341的评估，使用了3' - 错配引物。通过DNA测序确认了纯合野生型基因型NAT24/4。肺癌患者中快速乙酰化基因型占43.9%，对照患者中占41.6%（优势比为1.10；95%置信区间为0.73至1.65；无显著性差异）。将等位基因NAT24的纯合子和杂合子携带者区分开来后发现，肺癌患者中NAT24/4基因型明显过多（优势比为2.36；95%置信区间为1.05至5.32；P = 0.018）。考虑性别、年龄和吸烟情况的逻辑回归分析得出优势比为3.04（95%置信区间为1.37至6.75；P = 0.003）。因此，具有特别高乙酰化能力的NAT24/*4基因型携带者患肺癌的风险显著增加。
