Detection of risk of cancer to man

Our plain-English summary of Detection of risk of cancer to man, by R. Peto (Proceedings of the Royal Society of London. Series B, Biological Sciences, 1979).

The study

• Author: R. Peto
• Journal: Proceedings of the Royal Society of London. Series B, Biological Sciences
• Published: 1979;205(1158):111-20
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 001043).

Abstract

Epidemiology can pick out large-scale determinants of human cancer, such as smoking. Also, epidemiology can pick out carcinogens such as asbestos to which groups of perhaps a few hundred or a few thousand workers have been heavily exposed for decades. However, if highly exposed groups cannot be studied then epidemiology cannot recognize carcinogens which, although perhaps widely distributed, produce only a small percentage increase in particular cancers. Almost all of the environmental pollutants that can affect human cancer incidence will do so only to a very minor extent, at the levels to which we are currently exposed. For this reason, and also because it is often difficult to define an exposed and an unexposed group which do not differ in other ways as well, it will almost always be impossible to do anything epidemiologically except to set a very crude upper limit on their likely hazards. The only way, therefore, to get any direct estimate of these hazards is by laboratory studies of the effects of high doses on various model systems. For this and for other reasons, it would be highly desirable to have good laboratory models for human carcinogenesis. The characteristics required of satisfactory laboratory systems are reviewed, and it is argued that systematic errors may arise unless one studies epithelial cells from large, long-lived species under conditions of chronic, low-dose exposure to noxious test agents in conjunction with standard chronic doses of agents which may be synergistic with the test agents. (Carcinogenic mutagens may be synergistic with carcinogenic non-mutagens.) For reasons of expense and speed, such studies must be done in vitro. If such in-vitro systems can be developed, either by using tissue explants or cell cultures, an important criterion which they will have to satisfy to be trusted will be that under chronic exposure the rate of transformation should be proportional to something like the fourth power of exposure duration. This paper chiefly reviews the reasons for choosing these specifications for a trustworthy in-vitro model for human carcinogenesis.

In plain English

This article was a paper given at a discussion meeting. In it the author made a theoretical argument; it was not a new study of people or animals. Asbestos appeared only as an example: the author wrote that epidemiology can pick out carcinogens such as asbestos when groups of perhaps a few hundred or a few thousand workers have been heavily exposed for decades. The author argued that epidemiology can rarely monitor a 10% increase in hazard reliably, so small effects of widespread pollutants would have to be studied in the laboratory. The author stated that carcinomas, which are cancers of epithelial cells, make up about 90% of human cancer. The author stated that cancer risk depends much more strongly on how long exposure lasts than on the daily dose. The author proposed in-vitro models (cell cultures or tissue samples grown outside the body) using epithelial cells from large, long-lived species under chronic low-dose exposure, saying this was needed for reasons of expense and speed. The author acknowledged that these multi-stage model arguments were only theoretical and might be seriously misleading.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Theoretical review and discussion paper from a symposium, followed by a published discussion with B. A. Bridges; no new data were collected
• Who was studied: No study population. The author drew on general cancer statistics, including British fatal cancer figures, and on other published work
• Exposure: Asbestos was mentioned only as an example of a carcinogen that epidemiology can detect in heavily exposed groups of workers. The paper is mainly about chronic low-dose exposure to carcinogens and environmental pollutants in general
• Main results:
  • The author argued that epidemiology can usually detect twofold relative risks when exposed and unexposed groups can be clearly identified, but can rarely monitor a 10% increase in hazard reliably
  • The author stated that carcinomas account for about 90% of human cancer. According to the author, 20% of fatal British cancers are carcinomas of sex-specific organs and 70% are carcinomas of other epithelia
  • The author stated that, for most carcinomas other than those of sex-specific organs, incidence rates rise roughly in proportion to the 4th, 5th or 6th power of age
  • The author argued that cancer risk depends much more strongly on how long exposure lasts than on the daily dose rate
  • The author estimated that, at the same age, a single human epithelial cell is more than a billion (10 to the 9th power) times less likely than a mouse epithelial cell to give rise to a carcinoma
  • The author proposed studying epithelial cells from large, long-lived species under chronic, low-dose exposure. The author argued that for reasons of expense and speed such studies must be done in vitro, using tissue explants or cell cultures
  • The author proposed that a trustworthy in-vitro model should show cell transformation rates rising in proportion to roughly the fourth power of exposure duration
• The authors' conclusion: The author concluded that current in-vitro testing methods may systematically miss classes of human carcinogens. The author argued that laboratory models should use epithelial cells from species with a lifespan and body mass comparable to humans
• Limitations the authors state:
  • The author acknowledged that the multi-stage model arguments used are only theoretical and may be seriously misleading
  • The author wrote as a self-described complete outsider to laboratory research

Topics

Medical terms in this study, explained in our Lexicon: Epidemiology, Carcinogenesis, Carcinogenic.

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