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.
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