Increased frequency of a null-allele for NAD(P)H: Quinone oxidoreductase in patients with urological malignancies
Increased frequency of a null-allele for NAD(P)H: Quinone oxidoreductase in patients with urological malignancies
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DOI：
10.1097/00008571-199706000-00008
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发表时间：
1997-06-01
期刊：
影响因子：
--
通讯作者：
Sies, H
中科院分区：
文献类型：
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作者：
Schulz, WA;Krummeck, A;Sies, H
染色体16q2.2上的NQ 01基因座编码NAD（P）H：醌氧化还原酶，一种涉及解毒和保护免受氧化还原循环的酶，在人群中已经鉴定出两种等位基因，较罕见的一种，称为无效等位基因，编码无功能酶。由于已经表明缺乏NQOR活性会增加对某些癌症的易感性，通过聚合酶链反应-限制性片段长度多态性分析确定这两种等位基因在肾细胞癌（n = 131）和尿路上皮癌（n = 99）患者中的分布，并与正常人群（n = 260）进行比较，等位基因在正常人群中的分布遵循Hardy-Weinberg分布，主等位基因的频率为0.867，无效等位基因的频率为0.133。在肿瘤患者组中，由于纯合子和杂合子的数量增加，零等位基因的频率增加（分别为0.191和0.182）。肾细胞癌和尿路上皮癌的纯合子空等位基因与野生型基因型的比值比分别为1.7和3.6。这些数据与以下假设一致，即某些个体中NQOR活性降低会增加对某些癌症的易感性。
The NQ01 locus on chromosome 16q2.2 encodes NAD(P)H:quinone oxidoreductase, an enzyme implicated in detoxication and protection against redox cycling, Two alleles have been identified in the human population, the rarer one, termed the null-allele, coding for a nonfunctional enzyme, Since lack of NQOR activity has been suggested to increase susceptibility to certain cancers, the distribution of the two alleles was determined by polymerase chain reaction-restriction fragment length polymorphism analysis in patients with renal cell carcinoma (n = 131) and urothelial carcinoma (n = 99) compared with a normal population (n = 260), Allele distribution in the normal population followed a Hardy-Weinberg distribution with frequencies of 0.867 for the major allele and 0.133 for the null-allele. Increased frequencies of the null-allele were found in the tumour patient groups (0.191 and 0.182, respectively) due to an increased number of both homo- and heterozygotes. The odds ratios for homozygous null-allele vs, wild-type genotypes were 1.7 and 3.6 for renal cell carcinoma and urothelial carcinoma, respectively, These data are compatible with the assumption that diminished activity of NQOR in some individuals increases susceptibility to certain cancers.