Instructor: Hi, everyone.
In today's lecture,
we will continue discussing the epidemiology of lung cancer
by digging into the Surgeon General's 1964 Report
and the history of tobacco control in the US.
So our two aims of this presentation
are to review the early studies of smoking and lung cancer
and to describe the Surgeon General's 1964 Report.
So before we begin, I just wanna circle back
and remind everyone about Hill's criteria of judgment.
And these were the criteria that was promulgated
by Bradford Hill, a British statistician,
in the mid 20th century.
The key components of the criteria of judgment
are the consistency of independent studies.
That being that consistent findings observed
by different people in different places
with different samples are all pointing
to the same conclusions.
That is, the studies are reproducible.
The strength of association
is another important aspect to look at
when trying to determine
whether something is a causal relationship.
And that means that if there's only a small association
between a proposed cause and proposed effect,
that does not mean that there's not a causal effect,
but the larger the association,
the more likely that it is causal.
The biological gradient,
or the dose response relationship,
says that greater exposure should generally lead
to greater incidence of the effect.
However, in some cases,
the mere presence of the factor can trigger the effect.
So there may be no gradient.
Specificity is also important.
Causation is likely if there is a very specific population
at a specific site and disease
with no other likely explanation.
The more specific an association between a factor
and an effect is,
the bigger the probability
of a causal relationship.
Next, we have the importance of temporality.
So that states that the effect has to occur after the cause
and if there's an expected delay
between the cause and the expected effect,
then the effect must occur after the delay.
Finally, we have coherence.
So there should be a coherence
between epidemiological and laboratory findings
in order to determine that there's an effect.
However, at the same time,
the lack of such laboratory evidence cannot nullify
the possibility or the presence of an epidemiological effect
on an association.
So keeping this criteria of judgment in mind,
we move to the state of smoking in 1964.
There were 70 million smokers in the US
and the per capita cigarette use had increased from 50
in 1910 to almost 4,000 in 1962.
Next, there's significant proportions of smokers in 1955.
So in 1955, it's projected that 68% of men smoked
and 38% of women smoked.
Next, we see too that there's an increase,
or an increased concentration of tobacco in cigars
and chewing tobacco.
So the tobacco that was present in 117 cigars in 1920
is equivalent to 55 in 1962.
Similarly, the amount of tobacco in two to four pounds
of chewing tobacco in 1900 could be found
in only a half pound of chewing tobacco in 1962.
So the Surgeon General's report
that was published in 1964 used
a number of different kinds of evidence.
There were animal studies,
there were clinical and autopsy studies,
and there were population studies.
So both cohort and case control studies.
The report found that there were three main classes
of carcinogens in tobacco smoke, heterocyclic amines,
nitrosamines, and polycyclic aromatic hydrocarbons.
The report drew upon seven prospective cohort studies
involving more than a million men.
These studies looked at the smoking history
and other characteristics of participants,
and there were 10 years of follow up.
Over that time period, there were almost 40,000 deaths,
and mortality rates in smokers and non-smokers were compared
to determine the excess deaths in smokers.
The study also adjusted for age.
So one category of study was autopsy studies,
and these studies looked at 63 men,
or 63 individuals who died from lung cancer
and 339 who died from causes other than lung cancer
at the Veterans Administration Hospital
in East Orange, New Jersey.
Smoking history were ascertained from the family
and the frequencies of histological changes observed
in smokers and non-smokers were compared.
Lung tissues from smoking cases
had significantly higher frequencies of carcinoma in situ,
squamous metaplasia, hyperplasia,
and loss of cilia than lung tissues
from non-smoking patients.
Furthermore, the frequency of lesions increased
with the level of smoking.
Among 65 men who never smoked regularly,
16.8% of 3,324 specimens showed
at least one histological change in the epithelium,
whereas one or more epithelial changes were found
in 98% of the 13,689 specimens
from 274 men who regularly smoked cigarettes
and diet of causes other than lung cancer,
and in 99.8% of the 2,784 specimens from the 63 men who died
of lung cancer.
Most notably, the frequency of carcinoma in situ,
or lung cancers, was 0% in non-smokers,
20% in those who smoked less
than one pack of cigarettes per day,
48% in those who smoked one to two packs per day,
and 75% in those who smoked more than two packs
of cigarettes per day,
and 83% in those who died from lung cancer.
Based on these results,
the investigators concluded the following.
"In our opinion,
the histologic evidence
from this study greatly strengthens
the already overwhelming body of epidemiologic evidence
that cigarette smoking is a major factor
in the causation of bronchogenic carcinoma.
So the Surgeon General's report came out
with some conclusions about smoking and health.
Overall, smoking leads to a 1.7 fold increase
in all cause mortality
and a tenfold increase in lung cancer mortality.
For heavy smokers,
there's a 20 fold increase in lung cancer mortality.
There's also increases in mortality
from other types of cancer and other chronic conditions.
So laryngeal cancer,
smokers had a fivefold increase
in mortality when compared to non-smokers.
For COPD, it's a sixfold increase,
and for CBD it's a twofold increase.
So in the wake of the Surgeon General's report,
several steps were taken to control tobacco
and tobacco use in the US.
Smoking prevalence peaked at 42% in 1964
and has dropped to 18% in 2013 in the US.
And tobacco control
has been prevented 8.3 million premature deaths in the US
since the 1964 report.
Clearly, the cause and effect patterns of smoking
and lung cancer are clearly visible
on examinations of ecologic time trend data in the US.
Here, we see that there's close parallels
of lung cancer mortality in cigarette use in the US
that has persisted since 1930.
The time interval between the exposure curve
and the mortality curve reflects
an approximate age development,
or an approximate average development time
of 20 years or more for lung carcinogenesis.
Overall, cigarette smoking accounts for 85 to 90%
of all lung cancer risk in the US
and most other developed countries.
Here too we see that there's different kinds
of carcinoma in the lung.
So people can be afflicted by a adenocarcinoma
or squamous cell carcinoma of the lung.
One causal factor that determines which cancer
that people become diagnosed with
is the kind of cigarette or tobacco that one is consuming.
So right now in the US,
filter brands now dominate the market
and currently comprise over 85%
of all cigarettes manufactured in the US.
Compared to non-filtered cigarettes,
filter brands deliver less tar and nicotine per cigarette.
And among smokers in the US,
about 96% of women and 92% of men smoke filter cigarettes.
Despite this transition to filter or low yield cigarettes,
smokers tend to inhale deeper
and compensate by smoking more cigarettes,
which may account for the drastic increase
in lung adenocarcinomas among cigarette smokers
in recent years.
Major changes have occurred in the profile
of histologic cell types of lung cancer being diagnosed
during the past several decades,
as evidenced by this chart,
and the increase in odds of adenocarcinoma
over squamous cell carcinoma.
So we can say that the changing histologic profile
of lung cancer is due to the transition from non-filtered
to filter cigarettes.
Finally, among men and women who smoked 30
or more cigarettes daily,
the odds of developing either squamous cell carcinoma
or small cell carcinoma were four to five times higher
than the odds of developing adenocarcinoma.
There were also differences in the histologic profile
of lung cancer in men and women
and among smokers versus non-smokers.
Among men, the majority of tumors, or 53%,
were squamous cell carcinomas,
and 20% were small cell carcinomas,
and 27% were adenocarcinomas.
Among women, the majority of tumors were adenocarcinomas,
and 28% were squamous cell carcinoma,
and 22 were small cell carcinoma.
So here we see that the odds ratio
of men having squamous cell carcinoma
is nearly 100 times higher among men who smoke 30
or more cigarettes per day
than those who don't smoke cigarettes per day.