Bitton Asaf, Neuman Mark D, Barnoya Joaquin, Glantz Stanton A
Center for Tobacco Control Research and Education, University of California, San Francisco, CA 94143, USA.
Lancet. 2005;365(9458):531-40. doi: 10.1016/S0140-6736(05)17871-4.
Mutations in the p53 tumour suppressor gene lead to uncontrolled cell division and are found in over 50% of all human tumours, including 60% of lung cancers. Research published in 1996 by Denissenko and colleagues demonstrated patterned in-vitro mutagenic effects on p53 of benzo[a]pyrene, a carcinogen present in tobacco smoke. We investigated the tobacco industry's response to p53 research linking smoking to cancer. We searched online tobacco document archives, including the Legacy Tobacco Documents Library and Tobacco Documents Online, and archives maintained by tobacco companies such as Philip Morris and R J Reynolds. Documents were also obtained from the British American Tobacco Company depository in Guildford, UK. Informal correspondence was carried out with scientists, lawyers, and tobacco control experts in the USA and Europe. We found that executives and scientists at the highest levels of the tobacco industry anticipated and carefully monitored p53 research. The tobacco industry's own scientists conducted research which appeared to cast doubt on the link between smoking and p53 mutations. Researchers and a journal editor with tobacco industry ties participated in the publication of this research in a peer-reviewed journal without clear disclosure of their tobacco industry links. Tobacco industry responses to research linking smoking to carcinogenic p53 mutations mirror prior industry efforts to challenge the science linking smoking and lung cancer. The extent of tobacco industry involvement in p53 research and the potential conflict of interest discussed here demonstrate the need for consistent standards for the disclosure and evaluation of such potential conflicts in biomedical research.
p53肿瘤抑制基因的突变会导致细胞分裂失控，在超过50%的人类肿瘤中都有发现，包括60%的肺癌。1996年丹尼森科及其同事发表的研究表明，烟草烟雾中的致癌物苯并[a]芘对p53有体外诱变作用。我们调查了烟草行业对将吸烟与癌症联系起来的p53研究的反应。我们搜索了在线烟草文献档案，包括遗产烟草文献库和在线烟草文献库，以及菲利普·莫里斯和雷诺兹等烟草公司维护的档案。文件还从位于英国吉尔福德的英美烟草公司资料库获取。我们与美国和欧洲的科学家、律师及烟草控制专家进行了非正式通信。我们发现，烟草行业高层的管理人员和科学家预见到了p53研究并对其进行了仔细监测。烟草行业自己的科学家开展的研究似乎对吸烟与p53突变之间的联系提出了质疑。与烟草行业有关联的研究人员和一名期刊编辑参与了这项研究在同行评审期刊上的发表，但并未明确披露他们与烟草行业的关联。烟草行业对将吸烟与致癌性p53突变联系起来的研究的反应，反映了该行业此前对质疑吸烟与肺癌之间科学联系所做的努力。本文所讨论的烟草行业在p53研究中的参与程度以及潜在的利益冲突表明，生物医学研究中需要有统一的标准来披露和评估此类潜在冲突。
