Hubbard A L, Moyes C, Wyllie A H, Smith C A, Harrison D J
Sir Alastair Currie CRC Laboratories, Department of Pathology, University of Edinburgh, Medical School, UK.
Br J Cancer. 1998 Mar;77(6):913-6. doi: 10.1038/bjc.1998.151.
Increased cancer risk has been associated with functional polymorphisms that occur within the genes coding for the N-acetyltransferase enzymes NAT1 and NAT2. We detected two NAT1 polymorphisms in colorectal cancer patients by heteroduplex analysis. DNA sequencing revealed the wild-type sequence (NAT14) and two single base substitutions at adjacent positions 999 bp (C to T, NAT114) and 1000 bp (G to A, NAT115) of the gene, changing Arg187 to a stop codon and Arg187 to Gln respectively. NAT1 alleles NAT14 (0.98) and NAT115 (0.02) were present at a similar frequency in patients with colorectal cancer (n=260) and in a Scottish control group (n=323). The third allele, NAT114, was present only in the colorectal cancer group at a frequency of 0.006. NAT1 genotype NAT14/ NAT115 was significantly less frequent in individuals that had a slow NAT2 genotype. This was observed in both cancer and control groups and suggests that this association was unrelated to cancer risk. We conclude that polymorphisms within the coding region of the NAT1 gene are infrequent and do not appear to have an independent association with colorectal cancer risk. However, the relationship between NAT1 and NAT2 polymorphisms appears non-random, suggesting a linkage between these enzymes.
癌症风险增加与编码N - 乙酰转移酶NAT1和NAT2的基因中出现的功能性多态性有关。我们通过异源双链分析在结直肠癌患者中检测到两种NAT1多态性。DNA测序揭示了野生型序列（NAT1 * 4）以及该基因相邻位置999 bp（C到T，NAT1 * 14）和1000 bp（G到A，NAT1 * 15）处的两个单碱基替换，分别将Arg187变为终止密码子和将Arg187变为Gln。NAT1等位基因NAT1 * 4（0.98）和NAT1 * 15（0.02）在结直肠癌患者（n = 260）和苏格兰对照组（n = 323）中的出现频率相似。第三个等位基因NAT1 * 14仅在结直肠癌组中以0.006的频率出现。NAT1基因型NAT1 * 4 / NAT1 * 15在NAT2基因型较慢的个体中频率显著较低。在癌症组和对照组中均观察到这一点，这表明这种关联与癌症风险无关。我们得出结论，NAT1基因编码区内的多态性很少见，似乎与结直肠癌风险没有独立关联。然而，NAT1和NAT2多态性之间的关系似乎不是随机的，表明这些酶之间存在连锁关系。
