在阿弗拉托克辛暴露后,肝细胞癌中p53突变
1Massachusetts General Hospital Cancer Center.
Lancet (London, England)
|November 30, 1991
概括
肝细胞癌 (HCC) p53基因突变,特别是在编码号249的突变,与阿弗拉托克辛暴露有关. 这种特定的突变确定了与饮食风险相关的肝癌的特有形式.
科学领域:
- 在瘤学瘤学.
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
背景情况:
- 肝细胞癌 (HCC) 是一种普遍存在的原发性肝癌.
- 在HCC中,p53瘤抑制基因经常发生突变.
- 特定的p53突变可能表明暴露于特定的致癌物质.
研究的目的:
- 为了确定HCC样本中的p53基因中249号码的热点突变的全球频率.
- 调查249号码头突变,地理位置和暴露于环境风险因素 (如亚毒素和乙型肝炎病毒 (HBV)) 之间的相关性.
主要方法:
- 来自14个国家的HCC样本的选,以检测p53编码子249热点突变.
- 分析基因突变频率与地理原产地和患有不同偏毒素暴露风险的患者群体的关系.
- 在HBV感染患者的突变率与高相比低的亚拉托克辛暴露率的比较.
主要成果:
- 在17% (12/72) 的南非和东南亚HCC瘤中检测到p53编码子249突变,但在北美,欧洲或日本的样本中没有检测到.
- 在全球范围内,在249突变的存在和对亚毒素和HBV的高风险暴露之间观察到强烈的相关性.
- 在感染HBV的患者中,53% (8/15) 来自非洲毒素高风险的莫桑比克有这种突变,相比之下,8% (1/12) 来自低风险的特兰西.
结论:
- p53编码子249突变是HCC的特有形式的标志物.
- 这种特定的突变与饮食中吃到的亚弗拉托克素有很强的关联,特别是在HCC流行率高的地区.
- 这些发现突显了环境致癌物在肝癌病因学中的作用.
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