Molecular epidemiology of VHL gene mutations in renal cell carcinoma patients:: relation to dietary and other factors
Molecular epidemiology of VHL gene mutations in renal cell carcinoma patients:: relation to dietary and other factors
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DOI：
10.1093/carcin/23.5.809
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发表时间：
2002-05-01
期刊：
影响因子：
4.7
通讯作者：
Lindblad, P
中科院分区：
文献类型：
--
作者：
Hemminki, K;Jiang, YW;Lindblad, P
致癌化学物质通过DNA损伤和有丝分裂作用起作用。没有现成的机制来解释食物，如蔬菜和水果的预防癌症的作用。如果有这样的数据，最好是关于肿瘤启动基因的，那么保护作用的证据就会变得更有力。von Hippel-Lindau （VHL）基因是一种易导致散发性肾细胞癌（RCC）和von Hippel-Lindau病的肿瘤抑制基因。我们之前在一项病例对照研究中分析了来自102名瑞典rcc患者的VHL突变，并在此研究了考虑突变类型的患者特征（包括饮食习惯和突变）之间的关联。结果以比值比（OR）给出，分别针对吸烟者和所有患者。在单变量分析中，食用蔬菜和柑橘类水果降低了吸烟者和所有患者中VHL突变的频率。在吸烟者特征的多变量分析中，焊接烟雾显示多种VHL突变的风险为5.63。在吸烟者中，柑橘类水果使GC与AT突变的比值降低到0.13，使多突变的比值降低到0.17；蔬菜使单突变的OR降低到0.22。在所有研究对象中，焊接烟雾是一个危险因素，柑橘类水果是一个保护因素。此外，硒的摄入可以防止多种突变。目前的研究结果提供了证据，表明蔬菜、硒，特别是柑橘类水果的摄入可以保护肾VHL基因免受内源性或人群中常见的突变损害。尽管大多数关联在生物学上是合理的，蔬菜和水果是一个先验的假设，但在这个相对较小的研究中，不能排除偶然的结果。
Carcinogenic chemicals act through DNA damage and mitogenic effects. No established mechanism explains the cancer preventive effects, if any, of food items, such as vegetables and fruit. If such data were available, preferably on tumor-initiating genes, the evidence for the protective effects would become stronger. The von Hipple-Lindau (VHL) gene is the tumor suppressor gene predisposing to both sporadic renal cell carcinoma (RCC) and von Hippel-Lindau disease. We have earlier analyzed VHL mutations in RCCs from 102 Swedish patients identified in a case-control study and here examine associations between patient characteristics, including dietary habits and mutations, considering the type of mutation. The results are given as odds ratios (OR), separately for smokers and all patients. In univariate analysis, consumption of vegetables and citrus fruit decreased the frequency of VHL mutations among smokers and citrus fruit among all patients. In multivariate analysis of smokers' characteristics, welding fumes showed a risk of 5.63 for multiple VHL mutations. In smokers, citrus fruit decreased the OR of GC to AT mutations to 0.13 and that of multiple mutations to 0.17; vegetables decreased the OR for single mutations to 0.22. Among all subjects, welding fumes were a risk factor and citrus fruit a protective factor. Additionally, an intake of selenium protected against multiple mutations. The present results provide evidence that the intake of vegetables, selenium and particularly of citrus fruit protects the renal VHL gene from mutational insults that may be endogenous or common in a population. Even though most of the associations are biologically plausible, and vegetables and fruit were an a priori hypothesis, fortuitous results cannot be ruled out in this relatively small study.