Bliley Lorillard
Part Three: State-of-the-Art Literature on Pulmonary Carcinogenesis
Abstract
Contains Part three of report on "State-of-the-art literature on pulmonary carcinogenesis, 1950 to 1966." Includes: "Chapters V. Statistical studies and surveys (topics 50 to 59, author index and 249 articles mailed January 28, 1992, pages 1 to 41); Chapter VI. Clinical and pathological studies of lung cancer; Chapter VII. Animal experiments on pulmonary carcinogenesis; Chapter VIII. Hostal susceptibility and environmental interactions; [and] Chapter IX. Smoking and lung cancer debate." Summarizes chapters on pages 5-7. Divides chapters by country-of-origin study topics with sub-listings of citations cataloged by unique industry identification numbers. Includes numbers of patients, controls, and ratios in each chapter, along with comprehensive citation cross-indexes. Duplicates Bates 2062775524.
Fields
- Type
- REPORT
- Author
- Aviado, Domingo M., M.D. (CTR Consultant; Special Projects Recipient)Dr. Aviado was a University of Pennsylvania professor and did work for tobacco companies. Dr. Aviado did secret dog inhalation studies in 1970s which were apparently covered up. Dogs were inhaling. No research papers were ever done, apparently (B.C. 7/7/94).
- Recipient
- Lorillard Counsel
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Pulmonary Carcinogenesis, January 16, 1992
Page 1
PART THREE: STATE-OF-THE-ART
LITERATURE ON PULMONARY CARCINOGENESIS
1950 to 1966
Introduction
Chapter V.
Statistical Studies and Surveys - Topics 50 to
59, Author Index and 249 articles mailed January
18, 1992, pages i to 41.
Chapter VI. Clinical and Pathological Studies of Lung Cancer
Chapter VII. Animal Experiments on Pulmonary Carcinogenesis
Chapter VIII. Hostal Susceptibility and Environmental
Interactions
Chapter IX.
Smoking and Lung Cancer Debate
Pulmonary Carcinogenesis, January 16, 1992
Page 2
INTRODUCTION
The literature on biomedical aspects of lung cancer became
more extensive during the 1950s and the 1960s. The total number
of articles published from 1950 to 1966 exceeded that published
during the first half of the century. The proliferation of
publications was not limited to lung cancer in particular but
applied in general to cancer and to all forms of lung diseases.
In spite of the increase in research activities, questions on
lung cancer etiology remained controversial because of lack in
consensus among proponents of extrinsic and intrinsic causes.
The conflicting opinions proposed prior to 1950 were intensified
through the second half of this century.
Proponents of smoking etiology of lung cancer have selected
the decade of the '50s as the beginning of research studies
favoring causal association between cigarette smoking and lung
cancer. When the United States Congress passed the Cigarette
Advertising and Labeling Act of 1966, several mono<~raphs and
reviews had already appeared, emphasizing the causal association
between cigarette smoking and lung cancer. The most wldely
quoted publlcatlons were those published under the auspices of
the Surgeon General of the United States Publlc Health Service
and the Royal College of Physicians. Their monographs reflect
the conflicting opinions among scientists llsted below.
Pulmonary Carcinogenesis, January 16, 1992
Page 3
Royal College of Physicians of London: Smoking and Health.
A report on smoking in relation to cancer of the lung and
other diseases (6203). It is my opinion that the Royal College
of Physician's report summarized the conflicting opinions more
effectively than the U. S. Surgeon General's Report. At the
outset, the summary quotations from the Smoking and Health of the
Royal College of Physicians of London need to be recalled as
follows:
There has been a great increase in deaths from this
disease in many countries during the past 45 years.
Some of this increase may be due to better dia~11osis,
but much of it is due to a real increase in incidence.
Men are much more often affected than women.
Surveys. Many comparisons have been made in
different countries between the smoking habits of
patients with lung cancer and those of patients of the
same age and sex with other diseases. A11 have shown
that more lung cancer patients are smokers, and more of
them heavy smokers than are the controls. The
association between smoking and lung cancer has been
confirmed by prospective studies in which the smoking
habits of large numbers of men have been recorded and
their deaths from various diseases observed
subsequently. All these studies have shown that death
rates from lung cancer increase steeply with increasing
consumptions of cigarettes. Heavy cigarette smokers may
have thirty times the death rate of non-smokers. They
have also shown that cigarette smokers are much more
affected than pipe or cigar smokers and that those who
had given up smoking at the start of the surveys had
lower death rates than those who had continued to smoke.
Varlou~ criticis~s, based on po~lble errors of election
and of dia~no~ls, which ~i~nt have caused a spurious
association bet~en smoking and lun~ cancer in these
st~Etes, are discusaed, x x x
Pathology of Smokers' Lungs. Of three types of
lung cancer, only the two commoner types are associated
with smoking. The lungs of smokers without cancer show
changes of chronic irritation, of the sort which might
precede cancer, more often than the lungs of nonsmokers.
Pulmonary Carcinogenesis, January 16, 1992
Page 4
Interpretation of the Evidence. The association of
lung cancer with cigarette smoking is generally agreed
to be true but warlous possible explanations of thls
association other than that of ~ause add effect have to
be considered. These are: -
(i) that people who are going to get lung cancer
have an increased desire to smoke throughout
their adult lives:
(ii) that smoking produces cancer only in the lungs
of people who are in any case going to get
cancer somewhere in the body, so that smoking
determines on the site of the cancer:
(iii) that lung cancer affects people who would have
died of tuberculosis in former times but have
now survived with lungs susceptible to cancer:
(iv) that smokers inherit their desire to smoke and
with it inherit a susceptibility to some other
undiscovered agent that causes lung cancer:
(v) that smokers are by nature more liable to many
diseases, including lung cancer, than the
"self-protective. minority of non-smokers:
(vi) that smokers tend to drink more alcohol than_
non-smokers so that drinking and not smoking
may cause lung cancer:
(vii) that motor car exhausts, or -
(viii) that generalized air pollution may render the
lungs of smokers more liable to cancer.
None of these explanations fits all the facts as
well as the obvious one that smoking is a cause of lung
cancer. There are other causes, Inclodlng air pollution
and substances whichmey be met in a few o~cupatlons,
but none of them is of such general importance as
smoking.
There are a few facts which may be considered to
conflict ~ith this conclusion namely: -
(i) that lung cancer o~cttrs Im only a ~ImorltF of
smokers:
(ii) that death rates from this disease are l~r
In m~me (~untrles than would be expected from
their cigarette consumption:
(ill) that there Is some confllcting evidence on the
effects of Inhalation of smoke:
(iv) that mo animal has yet been given lumq cancer
by exposure to cigarette smoke.
Conclusion. These facts are discussed and none of
them is found to contradict the conclusion that
cigarette smoking is an important cause of lung cancer.
P~Imonary Carcinogenesis, January 16, 1992
Page 5
If the habit ceased, the number of deaths caused by this
disease should fall steeply in the course of time.
[page $3 to $5 (6203)]
The above summary quotations do not contain reference
paragraphs and figures. Instead, I have highlighted in bold face
the phrases that are briefly reviewed in the text of the Report
of the Royal College of Physicians. The present State-of-the-Art
Review (of less than a hundred pages) has been grouped into five
chapters. Chapter V through Chapter IX include a" review of a
comprehensive check list of references that relate to the bold-
faced phrases, specifically:
Chapter V: Statistical Studies and Surveys - including
"various criticisms based on possible errors of
selection and of diagnosis, which.might have
caused a spurious association between smoking and
lung cancer in these studies."
Chapter VI: Clinical and Pathological Studies - with special
reference to environmental and occupational causes
• of lung cancer.
Chapter VII: Animal Experiments - with special emphasis to the
fact that "no animal has yet been given lung
cancer by exposure to cigarette s~oke," but
pulmonary carcinogenesis has been demonstrated in
experimental animals exposed to envlronmental and
occupational substances.
Pulmonary Carcinogenesis, January 16, 1992
Page 6
Chapter VIII:
Chapter IX:
Hostal Susceptibility Factors - relevant to
smokers who "have an increased desire to smoke
throughout their adult lives," and that "smoking
produces cancer only in the lungs of people who
are in any case going to get cancer somewhere in
the body."
Smoking and Lung Cancer Debate - among
epidemiologists, clinicians, pathologists, cancer
biologists, tobacco chemists, and committee
reports of government agencies, voluntary
organizations, and cigarette companies.
The above description of chapters is based on the fact that
concepts of pulmonary carcinogenesis during the first half of the
century, as well as through the 1950s and 1960s, were derived by
application of research techniques from various biomedical
disciplines. Human studies are exclusively reviewed in Chapters
V and VI whereas animal experiments are in Chapter VII; Chapter
VIII includes both human and animal observations. Each chapter
contrasts available information on cigarette smoking,
occupational hazards, and environmental pollution, to illustrate
the validity of a specific research technique In establishing
causation of lung cancer.
Chapters V to IX cover reviews of literature, not only to
cigarette smoking and lung cancer, but also of non-smoklng
Pulmonary Carcinogenesis, January 16, 1992
Page 7
factors, such as occupational/environmental factors and hostal
susceptibility. The evolution of a concept is discussed in the
words of the original investigator, followed by his own additions
and revisions, and then by collaborative and conflicting facts
and opinions. The usual pattern is for an original report
showing an association of cigarette smoking and lung cancer,
followed by other publications that usually interpret the
association to be causative in nature. An opposite pattern for
occupational and environmental factors evolved, i.e., a key
observation on their association with lung cancer was generally
interpreted to mean not causative in nature. Instead, lung
cancer was attributed to cigarette smoking and other personal
habits.
Surgeon General Reports.
Although I have used a Report of the College of Physicians
of London (6203) as a model summary statement on smoking and
lung cancer, the Report of the Advisory Committee to the Surgeon
General of the Public Health Service (6402) need to be recalled
in this Introduction. The conclusions on the section entltled
"Lung Cancer" are as follows:
1. Cigarette smoking is casually related to lung
cancer in men; the magnitude of the effect of
cigarette smoking far outweighs all other factors.
The data for women, though less axtenslve, point in
the same direction.
2. The risk of developing lung cancer increases with
duration of smoking and the number of cigarettes
Pulmonary Carcinogenesis, January 16, 1992
Page 8
smoked per day, and is diminished by discontinuing
smoking.
The risk of developing cancer of the lung for the
combined group of pipe smokers, cigar smokers, and
pipe and cigar smokers is greater than in non-
smokers, but much less than for cigarette smokers.
The data are insufficient to warrant a conclusion
for each group individually. [page 196 (6402)]
The "all other factors" outweighed by effect of cigarette smoking
were discussed in the text of the report, such as:
constitutional hypotheses, occupational hazards, previous
respiratory infections, coffee drinking, alcohol consumption,
nutritional status, and beer drinking. The conclusions that
"effect of cigarettesmoking far outweighs all other factors" was
not accepted by those who were conducting studies on occupational
and environmental causes.
Although the 1964 Report of the Surgeon General limited the
causal association between cigarette smoking and lung cancer in
men only, the 1972 Report went further: "cigarette smoking is a
cause of lung cancer in women but accounts for smaller proportion
of cases than in men" (7201). The 1982 Report of the Surgeon
General devote~ to cancer the summary statement was "cigarette
smoking is the major cause of lung cancer in the United States"
(8201). After 1966, there has been additional support for
occupation and environmental causes of lung cancer that
strengthen the non-smoklng etiology of lung cancer that were
known earller. The recent developments (after 1966) are not
included in this State-of-the-Art review.
Pulmonary Carcinogenesis, January 16, 1992
Page 9
For various reasons discussed with Ms. Vicky Thompson, the
text portion of Part Three has been omitted. Instead, the
submission consists of checklists of literature collected for
Chapters V to IX. The articles were collected using the same
strategy described in Part One, page 1 to 17, submitted January
Ii, 1989. The first two digits of the articles are according to
year of publication and the last two digits represent order of
acquisition or alphabetical arrangement. Since some years had
more than a hundred publications, the fourth digit has been
replaced by an alphabet. Thus, 609T represents the 121st article
listed for 1960. Fin-ally, it should be noted that provisional
Chapters V to IX have been altered to Topic Numbers as follows:
Chapter V to Topics 50 to 59;
Chapter VI to Topics 60 to 60;
Chapter VII to Topics 70 to 79;
Chapters VIII to Topics 80 to 90; and
Chapter IX to Topic 90 to 99.
References for Introduction to Part Three.
(6203) Royal College of Physicians. Smoking and Health. Pitman
Medical, London, 1962.
(6402) US Public Health Service. Smoking and Health. Report of
the Advisory Committee to the Surgeon General of the
Public Health Service. US Public Health Service
Publication No. 1103, 121-256, 1964.
(7201) US Public Health Service. The Health Consequences of
Smoking. A report of the Surgeon General, 1972. USDHHS-
PHS, Rockville, MD 1972.
(8201) US Public Health Service. The Health Consequences of
Smoking. Cancer. A report of the Surgeon General, 1982.
USDHHS-PHS, Rockville, MD 1982.
Pulmonary Carcinogenesis, January 16, 1992
Page 10
CHAPTER V. STATISTICAL STUDIES AND SURVEYS - Topics 50 to 59.
The Topics are identified as Retrospective or Prospective,
and American or foreign. All available articles written by each
epidemiologist have been retrieved by consulting literature
indices. Computerized searches did not become available until
1964/1965 so that titles were obtained from sources listed in
Part One. The Topics for Chapter V are as follows:
Topic 50. Epidemiologic studies on lung cancer in cigarette
smokers, 4 articles;
Topic 51. Retrospective studies in the United States, 59
articles;.
Retrospective-studies in Contlnental Europe, 17 -
articles;
Retrospective studies in Japan and Australia, 6
articles;
Retrospective studies in Great Britain, 24 articles;
Prospective studies of British doctors, 19 articles;
Prospective studies sponsored by the American Cancer
Society, 46 articles;
Prospective studies of U.S. Veterans, 14 articles;
Canadian prospective studies on smoking and health, 2
articles.
Topic 52. Retrospective studies and animal experiments by Wynder
and associates, 54 articles.
There are 249 articles for the Introduction and Topics 50 to 59.
Topic 53.
Topic 54.
Topic 55.
Topic 56.
Topic 57.
Topic 58.
Topic 59.
