Risch A, Wallace D M, Bathers S, Sim E
Department of Pharmacology, University of Oxford, UK.
Hum Mol Genet. 1995 Feb;4(2):231-6. doi: 10.1093/hmg/4.2.231.
Bladder cancer is a common multifactorial disease and is known to be associated with occupational exposure to arylamines. Smoking is also a recognised contributory environmental cause. Occupational bladder cancer has previously been associated with slow acetylation by N-acetyltransferase (NAT) in humans in phenotyping studies, but more recently there has been some controversy regarding this issue. NAT is an enzymic activity involved in the metabolism of arylamines, and its 'classical' polymorphism is due to multiple alleles at the NAT2 locus. A genotyping approach has been used to investigate NAT2 type in a population of 189 Caucasian bladder cancer patients attending a clinic at a hospital in Birmingham. Genomic DNA was prepared from a blood sample donated by each of the patients and was used in the polymerase chain reaction with primers specific for all NAT2 alleles. Restriction fragment length polymorphism analysis was used to determine which alleles were present. Results have been compared to those from an age-matched non-malignant Caucasian control population (59 individuals) from the same region. Occupational and smoking history was determined by questionnaire and a significant excess of genotypic slow acetylators is found in those groups of bladder cancer patients exposed to arylamines as a result of their occupation or who are cigarette smokers. A higher proportion of slow acetylators is also found in those bladder cancer patients without identified exposure to arylamines when compared to the non-malignant controls. Slow NAT genotype is therefore a contributory risk factor in bladder carcinogenesis which acts through influencing individual response to environmental carcinogens.
膀胱癌是一种常见的多因素疾病，已知与职业性接触芳基胺有关。吸烟也是公认的环境致病因素。在表型研究中，职业性膀胱癌以前被认为与人类N - 乙酰转移酶（NAT）的慢乙酰化有关，但最近关于这个问题存在一些争议。NAT是一种参与芳基胺代谢的酶活性，其“经典”多态性是由于NAT2基因座上的多个等位基因所致。采用基因分型方法对在伯明翰一家医院诊所就诊的189名白种人膀胱癌患者群体进行NAT2类型研究。从每位患者捐献的血液样本中制备基因组DNA，并将其用于与所有NAT2等位基因特异性引物的聚合酶链反应。采用限制性片段长度多态性分析来确定存在哪些等位基因。已将结果与来自同一地区年龄匹配的非恶性白种人对照群体（59人）的结果进行比较。通过问卷调查确定职业和吸烟史，结果发现，在因职业接触芳基胺或吸烟的膀胱癌患者组中，基因型慢乙酰化者显著过多。与非恶性对照组相比，在未发现接触芳基胺的膀胱癌患者中也发现较高比例的慢乙酰化者。因此，慢NAT基因型是膀胱癌发生的一个促成危险因素，它通过影响个体对环境致癌物的反应而起作用。
