EPIDEMIOLOGY
COURSE ASSIGNMENT 1
Cigarette Smoking and Lung Cancer
Question 1: What makes the first study a case-control study?
It is a case control study because it aimed at comparing the smoking habits of lung cancer patients with
the smoking habits of other patients that were unaffected by lung cancer admitted at the same hospital
at the same time. Patients admitted with a new diagnosis of lung cancer were interviewed by an
investigator on the basis of looking backward from the lung cancer disease to collect information that
will help determine the possible exposure that might have been the cause and compared with patients
hospitalized in the same hospital at the same time that were unaffected by the lung cancer disease to
analyze the occurrence of the possible cause among the cases and the comparison group.
Question 2: What makes the second study a cohort study?
It is a cohort because it aimed at recording cause of death among the British physicians in relation to
their smoking habit. Medical records were reviewed to identify exposure to a potential cause of disease
and death.
Question 3: Why might hospitals have been chosen as the setting for this study?
Because in the hospital you can find a lot of patients diagnosed with the diseases of interest and patients
with under conditions different from the condition under investigation.
Question 4: What other sources of cases and controls might have been used?
Cases and controls were also obtained from the vicinity (surrounding community).
Question 5: What are the advantages of selecting controls from the same hospitals as cases?
It is easy to find sufficient samples that are appropriate as required by the study
It is also easy to find sufficient samples without the disease been investigated but with similar exposure.
Question 6: How representative of all persons with lung cancer are hospitalized patients with lung
cancer?
Hospitalized patients with diagnosed lung cancer were randomly selected and those that meet the
inclusion criteria were further allowed to participate in the study and others were excluded based on the
set exclusion criteria.
Question 7: How representative of the general population without lung cancer are hospitalized patients
without lung cancer?
Samples from the general population without lung cancer who were both hospitalized patients and
those from the vicinity were also randomly selected and those that meet the inclusion criteria were
further allowed to participate in the study and others were excluded based on the set exclusion criteria.
Question 8: How may these representativeness issues affect interpretation of the study's results?
Some participants might not be fortunate to be interviewed because of death, discharge from hospital,
severity of illness, inability to understand the content of the questionnaire or can’t speak English.
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 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.
Cigarette smokers
Non-smokers
Total
Cases
1,350
7
1,357
Controls
1,296
61
1,357
Question 9: From this table, calculate the proportion of cases and controls who smoked.
Proportion smoked, cases:
1350/1357 = 0.99484156 = we then express in percentage 0.99484156*100 = 99.48% or rounded to
99.5% of cases that smoked for this study.
Proportion smoked, controls:
1296/1357 = 0.9550479 = then express in percentage 0.9550479*100 = 95.50% or rounded to 95% of
controls that smoked.
Question 10: What do you infer from these proportions?
The proportions of smoked 99.5% in cases and 95.5% in controls indicates a higher proportion of smoked
in both cases and controls which suggest that smoking was a common behavior among the participants
for this study and may have played a significant role in lung cancer incidence. In that regard, smoking
should be giving higher consideration as a relevant factor to consider when analyzing the study results.
Question 11a: Calculate the odds of smoking among the cases.
1350/7 = 192.85 or rounded to 192.9
Question 11b: Calculate the odds of smoking among the controls.
1296/61 = 21.24 or rounded to 21.2
Question 12: Calculate the ratio of these odds. How does this compare with the cross-product ratio?
The ratio of these odds
192.9/1 = 21.2/1
192.9/21.2 = 9.099 or rounded to 9.1.
Question 13: What do you infer from the odds ratio about the relationship between smoking and lung
cancer?
The calculated odds ratio above explains that people who smoke will be 9 times at risk of more likely to
develop lung cancer than those that do not smoke.
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 smokers
0
1-14
15-24
#cases
#controls
Odds Ratio
7
565
445
61
706
408
referent
6.97
9.51
25+
All Smokers
Total
340
1350
1357
182
1296
1357
16.29
9.08
Question 14: Compute the odds ratio by category of daily cigarette consumption, comparing each
smoking category to nonsmokers.
Category 1-14
Category 15-24
Odds in cases – 565/7 = 80.71
Odds in cases – 445/7 = 63.57
Odds in controls – 706/61 = 11.57
Odds in controls – 408/61 = 6.68
Odds Ratio – 80.71/11.57 = 6.97
Odds Ratio – 63.57/6.68 = 9.51
Category 25+
Category All Smokers
Odds in cases – 340/7 = 48.57
Odds in cases – 1350/7 = 192.85
Odds in controls – 182/61 = 2.98
Odds in controls – 1296/61 = 21.24
Odds Ratio – 48.57/2.98 = 16.29
Odds Ratio – 192.85/21.24 = 9.08
Question 15:
Interpret these results.
Category 1-14
The calculated odds ratio above explains that people in category 1-14 who smoke will be 6 times at risk
of more likely to develop lung cancer than those that do not smoke.
Category 15-24
The calculated odds ratio above explains that people in category 15-24 who smoke will be 9 times at risk
of more likely to develop lung cancer than those that do not smoke.
Category 25+
The calculated odds ratio above explains that people in the category 25+ who smoke will be 16 times at
risk of more likely to develop lung cancer than those that do not smoke.
Category All Smokers
The calculated odds ratio above explains that people in the category of all smokers will be 9 times at risk
of more likely to develop lung cancer than those that do not smoke.
Question 16: What are the other possible explanations for the apparent association?
The other possible association might be due to bias and no control mechanism for unknown factors.
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 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.
Question 17:
How might the response rate of 68% affect the study's results?
The 68% response rate is way below the acceptance level of 80% response rate which have the potential
to affect the validity of the study result in such a way that there might be bias involve in the process of
administering the questionnaire where in not everyone may have responded and also it might be
possible that those that do not give their response are more likely to have the outcome of interest.
The next section of this case study is limited to the analysis of male physician respondents, 35 years of
age or older.
The occurrence of lung cancer in physicians responding to the questionnaire was documented over a 10year 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.
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%
were from cytology, bronchoscopy, or X-ray alone; and only 1% were from just case history, physical
examination, or death certificate.
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.
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
0
1-14
15-24
25+
All smokers
Total
Deaths
from lung
cancer
Personyears
at risk
Mortality rate
per 1000
person-years
Rate
Ratio
3
22
54
57
133
136
42,800
38,600
38,900
25,100
102,600
145,400
0.07
0.57
1.39
2.27
1.30
0.93
referent
8.14
19.85
32.42
18.57
13.42
Rate
difference
per 1000
person-years
referent
0.5
1.32
2.2
1.23
0.86
Question 18: Compute lung cancer mortality rates, rate ratios, and rate differences for each smoking
category. What do each of these measures mean?
Category 1-14
Mortality rate – 22/38600*1000 = 0.57
Rate ratio – 0.57/0.07 = 8.14
Rate difference – 0.5
Category 15-24
Mortality rate – 54/38900*1000 = 1.39
Rate ratio – 1.39/0.07 = 19.85
Rate difference – 1.32
Category 25+
Mortality rate – 57/25100*1000 = 2.27
Rate ratio – 2.27/0.07 = 32.42
Rate difference – 2.2
Category All smokers
Mortality rate – 133/102600*1000 = 1.30
Rate ratio – 1.30/0.07 = 18.57
Rate difference – 1.23
Category Total
Mortality rate – 136/145400*1000 = 0.94
Rate ratio – 0.94/0.07 = 13.42
Rate difference – 0.86
Question 19: What proportion of lung cancer deaths among all smokers can be attributed to smoking?
What is this proportion called?
The lung cancer death proportion among all smokers is ~98% and the proportion is called Attributable
proportion.
Question 20: If no one had smoked, how many deaths from lung cancer would have been averted?
133 deaths could have been averted if no one had smoke.
Question 21: Which cause of death has a stronger association with smoking? Why?
Cardiovascular disease. It directly corresponds with an odds ratio of 9.51 under the mortality rate for
smokers and the odds ratio is greater than 1 which is an indication of strong association.
Question 24: What do these data imply for the practice of public health and preventive medicine?
The data indicates that smoking is strongly associated with lung cancer death and persons who smoke
are more likely to develop lung cancer and die than those that do not smoke. Preventive measures and
policies are needed to help minimize/eradicate the risk of lung cancer exposure.
Question 26:
What are the advantages and disadvantages of case-control vs. cohort studies?
Case control
Sample size
Cost
Study time
Rare disease
Rare exposure
Multiple exposure
Multiple outcome
Progression, spectrum of illness
Disease rates
Recall bias
Loss to follow up
Selection bias
Not expensive
short
Yes
No
No
Yes
No
No
Yes
No
Yes
Cohort
Large Sample size
Expensive
long
No
Yes
Yes
No
Yes
Yes
No
Yes
No
Question 27: Which type of study (cohort or case-control) would you have done first? Why? Why do a
second study? Why do the other type of study?
A case control study to have an insight on the possible cause of the disease and it is less time-consuming
compare to cohort which takes long time. The second study is needed to establish a clear relationship
between exposure and disease.
Question 28: Which of the following criteria for causality are met by the evidence presented from these
two studies?
Answer 28
YES
Strong association
Consistency among studies
Exposure precedes disease
Dose-response effect
Biologic plausibility
NO
Yes
Yes
Yes
Yes
No