Centers for Disease Control and Prevention
Epidemiology Program Office
Case Studies in Applied Epidemiology
No. 731-703
Cigarette Smoking and Lung Cancer
Student's Guide
Learning Objectives
After completing this case study, the participant should be able to:
G Discuss the elements of study design, and the advantages and disadvantages of
case-control versus prospective cohort studies;
G Discuss some of the biases that might have affected these studies;
G Calculate a rate ratio, rate difference, odds ratio, and attributable risk percent;
G Interpret each measure and describe each measure's main use; and
G Review the criteria for causation.
This case study is based on the classic studies by Doll and Hill that demonstrated a relationship
between smoking and lung cancer. Two case studies were developed by Clark Heath, Godfrey Oakley,
David Erickson, and Howard Ory in 1973. The two case studies were combined into one and
substantially revised and updated by Nancy Binkin and Richard Dicker in 1990. Current version
updated by Richard Dicker with input from Julie Magri and the 2003 EIS Summer Course instructors.
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
A causal relationship between cigarette smoking
and lung cancer was first suspected in the 1920s
on the basis of clinical observations. To test this
apparent association, numerous epidemiologic
studies were undertaken between 1930 and
1960. Two studies were conducted by Richard
Doll and Austin Bradford Hill in Great Britain.
The first was a case-control study begun in 1947
comparing the smoking habits of lung cancer
patients with the smoking habits of other
patients. The second was a cohort study begun
in 1951 recording causes of death among British
physicians in relation to smoking habits. This
case study deals first with the case-control study,
then with the cohort study.
Data for the case-control study were obtained
from hospitalized patients in London and vicinity
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over a 4-year period (April 1948 - February
1952). Initially, 20 hospitals, and later more,
were asked to notify the investigators of all
patients admitted with a new diagnosis of lung
cancer. These patients were then interviewed
concerning smoking habits, as were controls
selected from patients with other disorders
(primarily non-malignant) who were hospitalized
in the same hospitals at the same time.
Data for the cohort study were obtained from the
population of all physicians listed in the British
Medical Register who resided in England and
Wales as of October 1951. Information about
present and past smoking habits was obtained
by questionnaire. Information about lung cancer
came from death certificates and other mortality
data recorded during ensuing years.
Question 1: What makes the first study a case-control study?
Question 2: What makes the second study a cohort study?
The remainder of Part I deals with the case-control study.
Question 3: Why might hospitals have been chosen as the setting for this study?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
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Question 4: What other sources of cases and controls might have been used?
Question 5: What are the advantages of selecting controls from the same hospitals as cases?
Question 6: How representative of all persons with lung cancer are hospitalized patients with lung
cancer?
Question 7: How representative of the general population without lung cancer are hospitalized
patients without lung cancer?
Question 8: How may these representativeness issues affect interpretation of the study's results?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
Over 1,700 patients with lung cancer, all under
age 75, were eligible for the case-control study.
About 15% of these persons were not
interviewed because of death, discharge,
severity of illness, or inability to speak English.
An additional group of patients were interviewed
but later excluded when initial lung cancer
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diagnosis proved mistaken. The final study
group included 1,465 cases (1,357 males and
108 females).
The following table shows the relationship
between cigarette smoking and lung cancer
among male cases and controls.
Table 1. Smoking status before onset of the present illness, lung cancer cases and matched controls with
other diseases, Great Britain, 1948-1952.
Question 9:
Cases
Controls
Cigarette smoker
1,350
1,296
Non-smoker
7
61
Total
1,357
1,357
From this table, calculate the proportion of cases and controls who smoked.
Proportion smoked, cases:
Proportion smoked, controls:
Question 10: What do you infer from these proportions?
Question 11a: Calculate the odds of smoking among the cases.
Question 11b: Calculate the odds of smoking among the controls.
Question 12:
Calculate the ratio of these odds. How does this compare with the cross-product
ratio?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
Question 13:
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What do you infer from the odds ratio about the relationship between smoking and
lung cancer?
Table 2 shows the frequency distribution of male cases and controls by average number of cigarettes
smoked per day.
Table 2. Most recent amount of cigarettes smoked daily before onset of the present illness, lung cancer
cases and matched controls with other diseases, Great Britain, 1948-1952.
Daily number
of cigarettes
# Cases
0
# Controls
7
61
1-14
565
706
15-24
445
408
25+
340
182
All smokers
1,350
1,296
Total
1,357
1,357
Odds Ratio
referent
Question 14:
Compute the odds ratio by category of daily cigarette consumption, comparing each
smoking category to nonsmokers.
Question 15:
Interpret these results.
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
Although the study demonstrates a clear
association between smoking and lung cancer,
Question 16:
cause-and-effect is not the only explanation.
What are the other possible explanations for the apparent association?
The next section of this case study deals with the
cohort study.
Data for the cohort study were obtained from the
population of all physicians listed in the British
Medical Register who resided in England and
Wales as of October 1951. Questionnaires were
mailed in October 1951, to 59,600 physicians.
The questionnaire asked the physicians to
classify themselves into one of three categories:
1) current smoker, 2) ex-smoker, or 3)
nonsmoker. Smokers and
Question 17:
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ex-smokers were asked the amount they
smoked, their method of smoking, the age they
started to smoke, and, if they had stopped
smoking, how long it had been since they last
smoked. Nonsmokers were defined as persons
who had never consistently smoked as much as
one cigarette a day for as long as one year.
Usable responses to the questionnaire were
received from 40,637 (68%) physicians, of whom
34,445 were males and 6,192 were females.
How might the response rate of 68% affect the study's results?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
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The next section of this case study is limited to
the analysis of male physician respondents, 35
years of age or older.
were from cytology, bronchoscopy, or X-ray
alone; and only 1% were from just case history,
physical examination, or death certificate.
The occurrence of lung cancer in physicians
responding to the questionnaire was
documented over a 10-year period (November
1951 through October 1961) from death
certificates filed with the Registrar General of the
United Kingdom and from lists of physician
deaths provided by the British Medical
Association. All certificates indicating that the
decedent was a physician were abstracted. For
each death attributed to lung cancer, medical
records were reviewed to confirm the diagnosis.
Of 4,597 deaths in the cohort over the 10-year
period, 157 were reported to have been caused
by lung cancer; in 4 of the 157 cases this
diagnosis could not be documented, leaving 153
confirmed deaths from lung cancer.
Diagnoses of lung cancer were based on the
best evidence available; about 70% were from
biopsy, autopsy, or sputum cytology (combined
with bronchoscopy or X-ray evidence); 29%
The following table shows numbers of lung
cancer deaths by daily number of cigarettes
smoked at the time of the 1951 questionnaire
(for male physicians who were nonsmokers and
current smokers only). Person-years of
observation ("person-years at risk") are given for
each smoking category. The number of
cigarettes smoked was available for 136 of the
persons who died from lung cancer.
Table 3. Number and rate (per 1,000 person-years) of lung cancer deaths by number of cigarettes
smoked per day, Doll and Hill physician cohort study, Great Britain, 1951-1961.
Daily
number of
cigarettes
smoked
Deaths
from lung
cancer
Personyears
at risk
Mortality rate
per 1000
person-years
Rate
Ratio
Rate
difference
per 1000
person-years
0
3
42,800
0.07
referent
referent
1-14
22
38,600
15-24
54
38,900
25+
57
25,100
All smokers
133
102,600
Total
136
145,400
Question 18:
Compute lung cancer mortality rates, rate ratios, and rate differences for each smoking
category. What do each of these measures mean?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
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Question 19:
What proportion of lung cancer deaths among all smokers can be attributed to
smoking? What is this proportion called?
Question 20:
If no one had smoked, how many deaths from lung cancer would have been averted?
The cohort study also provided mortality rates for
cardiovascular disease among smokers and
nonsmokers. The following table presents lung
cancer mortality data and comparable
cardiovascular disease mortality data.
Table 4. Mortality rates (per 1,000 person-years), rate ratios, and excess deaths from lung cancer and
cardiovascular disease by smoking status, Doll and Hill physician cohort study, Great Britain, 1951-1961.
Mortality rate per 1,000 person-years
Attributable
risk percent
among
smokers
Smokers
Non-smokers
All
Rate ratio
Excess deaths
per 1,000
person-years
Lung cancer
1.30
0.07
0.94
18.5
1.23
95%
Cardiovascular
disease
9.51
7.32
8.87
1.3
2.19
23%
Question 21: Which cause of death has a stronger association with smoking? Why?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
In calculating the attributable risk percent, the
excess lung cancer deaths attributable to
smoking is expressed as a percentage of all lung
cancer mortality among all smokers. The
attributable risk percent of 95% for smoking may
be interpreted as the proportion of lung cancer
deaths among smokers that could have been
prevented if they had not smoked.
A similar measure, the population attributable
risk percent expresses the excess lung cancer
deaths attributable to smoking as a percentage
of all lung cancer mortality among the entire
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population. From a prevention perspective, the
population attributable risk percent for a given
exposure can be interpreted as the proportion of
cases in the entire population that would be
prevented if the exposure had not occurred. The
population attributable risk percent is often used
in assessing the cost-effectiveness and costbenefit of community-based intervention
programs.
One formula for the population attributable risk
percent is:
PAR% = (Incidence in entire population ! Incidence in unexposed) / Incidence in entire population
Question 22:
Calculate the population attributable risk percent for lung cancer mortality and for
cardiovascular disease mortality. How do they compare? How do they differ from the
attributable risk percent?
Question 23:
How many lung cancer deaths per 1,000 persons per year are attributable to smoking
among the entire population? How many cardiovascular disease deaths?
CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide
The following table shows the relationship
between smoking and lung cancer mortality in
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terms of the effects of stopping smoking.
Table 5. Number and rate (per 1,000 person-years) of lung cancer deaths for current smokers and exsmokers by years since quitting, Doll and Hill physician cohort study, Great Britain, 1951-1961.
Cigarette smoking status
Lung cancer
deaths
Rate per 1000
person-years
133
1.30
18.5
5
7
3
2
0.67
0.49
0.18
0.19
9.6
7.0
2.6
2.7
3
0.07
1.0 (ref)
Current smokers
For ex-smokers, years since quitting:
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