16.

17.

18,

19,

20.

21.

22.

23,

24,

. Knapp. D. E.. Domino, E. F. Action of nicotine on ascending reticular

activating system. Int J Neuropharmacol 1: 333-51, 1962.

3. Kuchle. H. J.. Loeser, A., Meyer, G., Schmidt, C. G., Strurmer, E. Ta.

bakrauch. Ein beitrag zur wirkung von tabakfeuchthaltemittein. 7

Ges Exp Med 118: 554-72, 1952.

. Laffan. R. J., Borison, H. L. Emetic action of nicotine and lobeline.

J Pharmacol Exp Ther 121: 468-76, 1957.

. Lambiase, M.. Serra, C. Fumo e sistema nervoso. 1, Modificazionj

dellattivita elettrica corticale da fumo. Acta Neurol (Napoli) 12.
475-93, 1957.

Langley, J. N. On the reaction of cells and of nerve-endings to certain
poisons, chiefly as regards the reaction of striated muscle to nicotine
and to curari. J Physiol (London) 33: 374-413, 1905.

Larson, P. S., Haag, H. B., Silvette, H. Tobacco. Experimental and
clinical studies. Baltimore, William & Wilkins, 1961. 932 p.

McKennis, H.. Jr. Special report to the Surgeon General’s Advisory
Committee on Smoking and Health.

Nicotine content of smoke from cigars and cigarets. [Queries and minor
notes] JAMA 130: 825, 1946.

Rapela, C. E., Houssay, B. A. Accién de la nicotina sobre la secrecién
de adrenalina y nos adrenalina de la sangre venosa suprarrenal del
perro. Rev Soc Argent Biol 28: 219-24, 1952.

Schnedorf, J. G., Ivy, A.C. The effect of tobacco smoking on the ali.
mentary tract. An experimental study of man and animals. JAMA
122: 898-904, 1939.

Silvette, H., Hoff, E. C., Larson, P. S., Haag H. B. The actions of nico-
tine on central nervous system function. Pharmacol Rev 14: 137-73,
1962.

Stumpf, C. Die wirkung von nicotin auf die hippocampustatigkeit des
kaninchens. Naunyn Schmiedeberg Archiv Exp Path 235: 421-36,
1959,

Thienes, C. H. Chronic nicotine poisoning. Ann NY Acad Sci 90:
239, 1960.
Chapter 8

 

Mortality
Contents

PROSPECTIVE STUDIES OF MALE POPULATIONS. .

Data on Smoking History .. 2... 1 6 + eee ee es
Adjustment for Differences in Age Distribution . .. . . .

RESULTS FOR TOTAL DEATH RATES .........

Mortality Ratios for Current Smokers... .-- 1+: |
Mortality Ratios by Amount Smoked .......-...
Mortality Ratios at Different Ages... .-- +e ees
Age at Which Smoking was Started . . . . -- eee s
Mortality Ratios by Duration of Smoking .......- .-
Inhalation of Smoke... 6 2 1 ee ee eee ee et
Ex-Cigarette Smokers . . 6. 6 ee ee ee es
Ex-Cigar and Pipe Smokers... . - 5 6 ee eee ees

EVALUATION OF SOURCES OF DATA .........

The Study Populations. ©... 6 6 ee ee ee ee
Non-Response Bias... - - - ee ee ee et es
Measurement of Smoking History... ... 6+ eee >
Stability of the Mortality Ratio. . . . 2. ee + eee

OTHER VARIABLES RELATED TO DEATH RATES. .

MORTALITY BY CAUSE OF DEATH ..........-
Results for Cigarette Smokers. . . . 2. - - ee eee
Mortality Ratios for Cigarette Smokers by Amount Smoked .

Cigarsand Pipes... - ee ee eet tt ee
The Contribution of Different Causes to Excess Mortality . .

SUMMARY .... 2... ee ee ee et ee ee

Total Mortality. 2. 6 6 ee ee ee ee et
Cigarette Smokers... 6 6 6 ee ee et te ts
Cigar Smokers «©. ee ee ee et et es
Pipe Smokers. 6. ee ee ee ee es

Mortality by Cause of Death . . ©. 2. ee ee ees

APPENDIX I

Appraisal of Possible Basis Due to Non-Response . .

APPENDIX II

Stability of Mortality Ratios. 2. 2 6. 6 ee ee eee
Assumptions . 1...) ee ee et es
The Binomial Approximation... - . 6... - +e
The Normal Approximation. . . 2... 6 - ee ees

REFERENCES. . 2... 6 1 ee ee ee ee ee es

78

108

122
1
112

113

li
111
118
119

120
FicureE 1.

Figure

Death rates (logarithmic scale) plotted against age

for current cigarette smokers and non-smokers, U.S. veterans

study . 2... ....--2004.,
List of Tables

Taste 1. Outline of prospective studies of smoking and mortality .

Taste 2. Mortality ratios of current smokers by type of
smoking

TaBLE 3. Mortality ratios for current it smokers of cigarettes only,
by amount smoked . ...........2.,

Taste 4. Mortality ratios for current smokers of oe only, by
amount smoked... ........2.2..

TaBLe 5. Mortality ratios for current smokers of pipes only, by
amount smoked .

TABLE 6. Mortality ratios by age group for current t smokers of
cigarettes only, men in 25 States. . 2... 2.

TABLE 7. Increase in natural logarithm of death rate per 1,000
man-years for each 5-year increase in age, 6 prospec-
tive studies. 2. 2 ee

TaBLe 8. Mortality ratios by age at which smoking was started
and by amount smoked for current smokers of
cigarettes only . So ee

TaBLe 9. Mortality ratios for current smokers by type of smoking
and by length of time smoked .. . . . 2... 1...

TaBLe 10. Mortality ratios for smokers of cigarettes only by
inhalation status and amount of smoking .

Taste 11. Mortality ratios for ex-smokers and current smokers of
cigarettes. 2 6... es

Taste 12. Mortality ratios for ex-smokers of cigarettes only by
number of years since smoking was stopped and by
amount smoked... ..........0008.

TaBie 13. Mortality ratios for ex-cigarette smokers by number
of years of smoking, U.S. veterans study .

TaBLe 14. Mortality ratios for ex-smokers of cigars only and
pipes only and for current cigar and pipe smokers .

Taste 15. Age-adjusted death rates per 1,000 man-years for
current smokers of cigarettes only (aged 35 and over),
by amount smoked, in seven studies and for U.S.
white males... 2... 1 ee een

Taste 16, Percentages of usable replies in five studies . .

Taste 17, Mortality ratios for cigarette smokers by population-
sizeofcity ........

TABLE 18, Age-adjusted death rates per 1, 000 (over approximately
22 months) for variables that may be related to
mortality. 2... .....04.

14-422 0-647

Page

88

83

86
36
87

87

89

89
90
91

93

93
93

94

95
96

99

100
TasB_e 19.

TaB_Le 20.

TaBLe 21.
TABLE 22,

TABLE 23.

TABLE 24,
TABLE 25.

TABLE 26.

TABLE 27.

TABLE 28.

TABLE 29,

Tape 30.

Total numbers of expected and observed deaths and
mortality ratios for smokers of cigarettes only in
seven prospective studies... .... hee

Expected and observed deaths and mortality ratios for
current smokers of cigarettes and other (three
studies) and for ex-cigarette smokers (four studies) .

Mortality ratios for coronary artery disease for smokers
of cigarettes only by amount smoked . no

Lung cancer mortality ratios for current smokers of
cigarettes only by amount smoked. . . . . . , ,

Expected and observed deaths and mortality ratios for
current cigarette smokers, for selected causes of
death, by amount smoked, in six studies rn

Numbers of expected and observed deaths and mortal-
ity ratios for cigar and pipe smokers, in five studies .

Percentage of total number of excess deaths of cigarette
smokers due to different causes re

Numbers of expected and observed deaths for smokers
of cigarettes only, and mortality ratios, each prospec-
tive study and all studies. 2... 1D. ve

Age-adjusted death rates (per 1,000 person-years) for
1954 respondents, 1957 respondents, and non-
respondents in U.S. veterans study... . 2...

Mlustration of calculation of non-response bias. . .

Mortality ratios in respondents and computed values
for the complete population. . . 2... 4...

Proportions and death rates for Berkson’s example . .

Page

102

105
106

106

106
107

108

109

114
115

116
116
 

Chapter 8

 

PROSPECTIVE STUDIES OF MALE POPULATIONS

The principal data on the death rates of smokers of various types and
of nonsmokers come from seven large prospective studies of men. In such
studies, information about current and past smoking habits, as well as
some supplementary information (e.g., on age), is first obtained from the
members of the group to be studied. Provision is also made to obtain
death certificates for all members of the group who die during subsequent
years. From these data, over-all death rates and death rates by cause are
computed for the different types of smokers, usually in five-year age classes.

These seven studies comprise all the large prospective studies known to
us. The first started in October 1951: the latest, in October 1959,

In brief, the seven groups of men are as follows:

{1) British doctors, a questionnaire having been sent to all members of

the medical profession in the United Kingdom by Doll and Hill,
1956 (5).

(2) White American men in nine states. These men were enrolled by a
large number of American Cancer Society volunteers, each of
whom was asked to have the questionnaire filled in by 10 white
men between the ages of 50 and 69. Hammond and Horn, 1958
(10).

(3) Policyholders of U.S. Government Life Insurance policies, available
to persons who served in the armed forces between 1917 and 1940.
Dorn, 1958 (6).

(4) Men aged 35-64 in nine occupations in California who were sus-
pected of being subject to a higher than usual occupational risk of
developing lung cancer. Dunn, Linden and Breslow, 1960 (7).

(5) California members of the American Legion and their wives. Dunn,
Buell and Breslow (8).

(6) Pensioners of the Canadian Department of Veterans Affairs, ie., vet-
erans of World Wars I and II and the Korean War. Best, Josie
and Walker, 1961 (2).

{7) American men in 25 states, enrolled by volunteer researchers of the
American Cancer Society, each of whom was asked to enroll about
10 families containing at least one person over 45. Hammond,
1963 (11).

It will be noted that the studies cover different types of population groups
in three countries. Study (2), often referred to as the Hammond and Hom
study, terminated after 44 months’ follow-up, and the data discussed here
for this study are essentially the same as those already published (10).
All other studies have accumulated substantial amounts of data beyond
that which has been published. The authors and agencies responsible for

81
the studies supplied their latest available data for this report. The tables
in this Chapter are based on the new compilations.

Table I shows for each study the approximate number of subjects from
whom usabie replies about smoking habits were obtained, the date of en-
rollment, age range, number of. months followed, total number of deaths,
and the number of person-years of exposure. The number of subjects
studied (usable replies) ranged from around 34,000 in the British doctors
study to 448,000 in the n&8w American Cancer Society study. The number
of months of follow-up varied from about 22 to 120.

Although several of the studies obtained some data on women, only the
California Legion study (8) and the new American Cancer Society study
(11) include large numbers of women. No tabulations on women are as
yet available from these prospective studies.

Data ON SMOKING HIsTorRyY

The exact description of the type of smoking and the amount smoked at
all times throughout a man’s past life would necessitate an amount of detail
and an accuracy of memory that was not considered practieable in these
studies. While the information collected on smoking habits varied from
study to study, all studies asked for data on the current amount and type of
smoking as of the date of answering the questionnaire. These amounts
were usually expressed as the number of cigarettes, cigars or pipes per day.
In the case of subjects who had stopped smoking previous to the date of
enrollment (ex-smokers}, most studies obtained data on the maximum
amount previously smoked per day. The category described as non-smokers
sometimes included also those men who had smoked an insignificant total
amount during their whole previous lifetime.

As regards type of smoking, cigarettes, cigars and pipes appear in all
seven combinations. Since results for the “mixed” categories are difficult to
interpret and sometimes involve relatively small numbers of subjects, the
analysis here concentrates on the following types:

Cigarettes only

Cigarettes and other

Cigars only

Pipes only
In some instances the last two categories have been combined when the num-
bers of subjects are too small to give reliable data for the separate types.

ADJUSTMENT FOR DIFFERENCES IN AGE DISTRIBUTION

Since the death rate of any group of men is markedly affected by their age
distribution, it is essential, when comparing the death rates of two groups of
men, to ensure that their age distributions are comparable. A standard meas-
ure for this purpose is the age-specific death rate, in which the rate is com-
puted for a group of men whose ages all lie within a relatively narrow span,
say 50-54 years. This measure is particularly appropriate when it is desired
to examine how the relative death rates in two groups change with age.

82
€8

TABLE 1.—Ouitline

of prospective studies of smoking and mortality

 

Authors

Doll & Hill (5)

Hammond &
Horn (10)

Dorn (6)

Dunn, Linden,
Breslow (7)

Dunn, Buell,
Breslow (8)

Best, Josie, Walker
(2)

Iiammond (11)

 

Subjects

British doctors

White men in 9
States

U.S, veterans

California occu-
pational groups

California Ameri-
can Legion mem-

Canadian pensioners
(veterans and de-

Men in 25 States

 

 

 

 

 

 

bers pendents)

Number of usable replies | 34,000 188,000 248,000 67,000 60,000 78,000 448,000
Date of enrollment Oct. 1951 Jan.-Mar. 1952 Jan, 1954 and Nov. 1953 and May-Nov. 1957 Sept. 1955-July, 1956 Oct. 1950-Feb.

Jan. 1957. May 1957. 1960.
Age range 35-75+ 50-69 30-75+ 39 35-754 35-754 35-89
Months followed 120 44 78 About 48 ~ About 24 72 About 22
Number of deaths 4,534 11,870 24,519 1,714 1,704 9,070 11,612
Person-years of exposure 269,000 668,000 1,312,000 222,000 119,000 383,000 820,000

 

 

 

 

 

 

 

 
Several methods of adjustment for differences in age distribution are
available for populations that have a wide range of ages. For comparing
the death rate of a group of smokers with that of the non-smokers in the
study, the measure most frequently used in previous publications is a type
of mortality ratio, obtained as follows: In each five-year age class, the age.
specific death rate for non-smokers is multiplied by the number of person-
years in the group of smokers. This product gives an expected number of
deaths, which represents the number of deaths of smokers that would be
expected to occur if the age-specific death rate were the same as for non.
smokers. These expected numbers of deaths are added over all age classes,
and their total is compared with the total number of observed deaths in the
smokers. The mortality ratio is the ratio (total observed deaths in the
smokers) /(total expected deaths). A mortality ratio of 1 implies that the
over-all death rates are the same in smokers and non-smokers after this
adjustment for differences in age distribution. It does not imply that the
death rates of smokers and non-smokers were the same at each specific age,
A mortality ratio higher than 1 implies that the group of smokers has a higher
over-all death rate than the non-smokers.

Another common method of adjustment for age is to use some age-
distribution as a standard, for instance the combined age-distribution of all
persons in the study or the age-distribution of the U.S. male population as
of a certain Census year. The age-specific death rates for a certain group
(e.g., smokers) are multiplied by the number of persons of that age in the
standard distribution. These products are added and finally divided by the
total standard population to obtain an age-adjusted rate for the group. A
mortality ratio of smokers to non-smokers is then computed as the ratio of
the age-adjusted rates for smokers and non-smokers. Mortality ratios com-
puted in different ways will of course give somewhat different results and
experts in this field do not regard any one method as uniformly best. In this
report we have used the ratio of observed to expected deaths, as described in
the previous paragraph, primarily because this measure is the most common
one in previous publications from these studies. Both methods of adjust-
ment run the risk of concealing a change in the relative death rate with age.
For instance, the over-all mortality ratio might be unity if smokers had higher
death rates than non-smokers prior to age 60, but lower death rates thereafter.

Smokers and non-smokers may differ with regard to variables other than
age that are known or suspected to influence death rates, such as economic
level, residence, hereditary factors, exposure to occupational hazards, weight,
marital status, and eating and drinking habits. In the summary results
to be presented in subsequent sections, as in most results previously pub-
lished, the death rates of smokers and non-smokers have not been adjusted
so as to equalize the effects of these disturbing variables. This issue will
be discussed later in this chapter.

A further complexity in interpreting the results comes from interrela-
tionships among the variables that describe the habit of smoking. As will
be seen, the death rates of a group of cigarette smokers vary with the amount
smoked, the age at which smoking was started, the duration of smoking, and
the amount of inhalation. In trying to measure the “net” effect of one of
these variables, such as the number of cigarettes smoked per day, we

84
should make adjustments so that the different groups of smokers being
compared are equalized on all other relevant aspects of the practice. This
can be done at best only partially. Most studies measured only some of the
variables on which adjustment is desirable. When the data are subclassi-
fied in order to make the adjustments, the numbers of deaths per subclass
are small, with the consequence that the adjusted death rates are somewhat
unstable.

Consequently, like previous reporters on these studies, we have used our
judgment as to the amount of subclassification and adjustment to present.
The possibility that part of the differences in death rates may be associated
with smoking variables other than the one under discussion cannot be
excluded.

RESULTS FOR TOTAL DEATH RATES

Morvatity Ratios ror CuRRENT SMOKERS

Table 2 shows the mortality ratios to non-smokers for men who were smok-
ing regularly at the time of enrollment.

For males smoking cigarettes only, the over-all death rate is higher than
that for non-smokers in all studies, the increase ranging from 44 percent
for the British doctors to 83 percent in the men in 25 states. For smokers
of other forms of tobacco as well as cigarettes the increases in death rates
are in all cases lower than for the smokers of cigarettes only.

For smokers of cigars only or of pipes only, three of the studies show small
increases in over-all death rates, ranging from 5 percent to 11 percent.
The study of men in 25 states, however, gives slight decreases for both types,
as does the British study for the two types combined.

TABLE 2.—Mortality ratios of current smokers by type of smoking

 

 

 

 

 

  

 

 

Study group?
Type of smoking | |
British Men in9 | U.S. vet- | Canadian | Men in 25
doctors States erans | veterans States
I

Cigarettes only__._....--_..-__--..-. 1.44 1.70 | 1.79 1.65 1,83

Cigarettes and other 1.05 1.45 | 1.46 1.23 1, 54

Cigars only__..____. 0.95 1.10 1.07 Lt 0.97

Pipes only__200 07707777277 2 1.05 | 1.06 | 1.10 0. 86
t

 

 

1 The California occupational and Legion studies give mortality ratios of 1.78 and 1,58 respectively, for
all cigarette smokers (current and ex-smokers).

Mortatity Ratios sy Amount SmMoKeEpD

For smokers of cigarettes only who were smoking at the time of entry,
the mortality ratio increases consistently with the amount smoked in each
of the seven studies, with one exception for the California occupational study,
which includes ex-cigarette smokers as well as current smokers (Table 3).

85
For smokers of cigars only who were smoking at the time of entry, four
of the studies give a breakdown into two amounts of smoking (Table 4).

Men smoking less than five cigars per day have death rates about the same
as non-smokers. For men smoking higher amounts there is some elevation
of the death rate. When the results are combined by adding the observed
and expected deaths over all four studies, an over-all mortality ratio of 1.20
is obtained for the five-or-more group. This over-all increase is statistically
significant at the 5 percent level.*

TaBLe 3.—Mortality ratios for current smokers of cigarettes only, by amount

 

 

smoked
Cigarettes per British Men in 9 U.S. California | California | Canadian | Men in 25
day doctors States veterans occupa- Legion* veterans States
tional* }
Less than 10..____ 1.06 1.33 1.35 1.44 } 21.30 { 1.55 1.45
10-20__-- 22-222. 1.31 1.66 1.76 1,79 . 1.68 1.75
21-39__-__------ 2. 31.62 Le 1.99 2,27 $1.64 51.84 { 1.90
40 and over... ___ 42.50 2.20 2,22 1.83 71,85 2,20

 

 

 

 

*Current and ex-cigarette smokers combined.

' ‘Less than 10” is ‘less than 5”’ plus “‘about 44"’; ‘‘10-20"' is “about 1’; “21-39” is “about 139”.
2 Less than 1 pack.

3 20-34,

435 plus.

5 More than 1 pack.

6 About 1 pack.

? More than 1 pack.

TABLE 4.—Mortality ratios for current smokers of cigars only, by amount

 

 

 

 

 

 

 

 

 

smoked
Number per day Men in 9 U.S. vet- | Canadian | Men in 25| Over-all
States erans veterans States results
It. ee enna eee 1.06 0. 99 1.12 0.93 1.00
5 or more__....--_--------2--2----- eee 1.20 1.24 71.26 1.10 1.20
11-2,
23 or more.

For current pipe smokers (Table 5), men smoking less than 10 pipefuls per
day have death rates very close to those of non-smokers. For heavy pipe
smokers (10 or more per day) two studies show increases of 15 and 12 per-
cent in death rates, but the other two studies show little or no increase. The
over-all mortality ratio of 1.05 does not differ statistically from unity. The

*Statistical significance throughout this report refers to the 5 percent level un-
less otherwise specified. In testing whether an observed mortality ratio of smokers
relative to non-smokers is greater than unity, the probability is calculated that a ratio
as large as or larger than the observed ratio would occur by chance if the smokers and
non-smokers were drawn from two populations having the same death rate. If this proba-
bility is less than 0.05 (5 percent) the observed increase in the death rate of smokers
relative to non-smokers is said to be statistically significant at the 5 percent level. The
results of significance tests will be quoted only for mortality ratios in which the number
of deaths raises a doubt as to whether the difference from unity could be due to sampling
errors.

86
British doctors study gives a mortality ratio of 0.91 for cigar and pipe smokers
together (presumably mostly pipe smokers) who consume more than 14 gms.
of tobacco daily.

TaBLE 5.—Mortality ratios for current smokers of pipes only, by amount

 

 

 

 

smoked
Study
Over-all
Pipes per day ratio
Men in 9 US. Canadian | Men in 25
States veterans veterans States
1-9-8. eo eee ee nee 1.00 1.03 1.07 0. 92 1.01
10 or more___...----- eee 1.15 1.12; 1.01 0.76 1.05

 

 

 

MortTa.ity Ratios aT DIFFERENT AGES

As indicated previously, the mortality ratios presented in previous tables
for different groups of smokers represent a kind of average over the age-
distribution of the smokers concerned, and do not necessarily apply to
smokers of any specific age. For cigarette smokers, the studies show that
the mortality ratio declines with increasing age, being higher for men aged
40-50 than for men over 70. This effect is illustrated in Table 6 from
the study of men in 25 states, which gives the mortality ratio computed
separately for five age classes.

The drop in mortality ratio with each increase in age appears fairly con-
sistently for every amount of smoking. For smokers of cigarettes only as a
whole, the death rate is more than double that for non-smokers in the age
range 40-49, but only about 20 percent higher for men over 80. The pic-
ture is, of course, different if we look at the absolute excess in death rates
at different ages. Owing to the marked increase in death rates with age, the
absolute excess also increases steadily with increasing age.

A more thorough investigation of the relation between death rates and
age for different groups of smokers has been made by Ipsen and Pfaelzer
(14). If the logarithm of the age-specific death rate is plotted against age,
the resulting points lie reasonably close to a straight line. For the U'S.

TaBLe 6.—Mortality ratios by age group for current smokers of cigarettes
only, men in 25 States

 

 

 

 

Age at start of study
Number of cigarettes per day
40-49 50-59 60-69 70-79 80-89
2. 27 1.44 1.40 1. 40 1.08
2,12 1.94 1. 60 1. 50 1.65
2.22 2.05 178 1, 48 1.16
3.06 2.37 1.68 1. 28 0. 58
2.33 2.06 1.70 1.47 1. 22

 

 

 

 

 

 

 

87
veterans study, Figure 1 shows the points and fitted lines for non-smokers
and for current smokers of cigarettes only. (The lines were fitted by the
standard method of least squares, weighting each point by the number of
deaths involved.)

If the lines for cigarette smokers and non-smokers were parallel, this
would imply that the mortality ratio of the smokers to the non-smokers Was
constant at all ages, because the vertical distance between the two lines at
any age is the log of the mortality ratio for that age. In Figure 1, however,

DEATH RATE (logarithmic scale) PLOTTED AGAINST AGE,
PROSPECTIVE STUDY OF MORTALITY IN U.S. VETERANS

900 (F

700

  

CURRENT CIGARETTE SMOKERS
500

400

300 F——

200

DEATH RATE PER 10,000 MAN-YEARS

100

  

NON-SMOKERS

 

AGE IN YEARS

Ficure 1.
the slope is slightly less steep for the cigarette smokers than for the non-
smokers. This indicates that the mortality ratio is declining with increased
age.

Table 7 shows these slopes (increase in the natural logarithm of the death
rate for each 5-year increase in age) computed from six of the studies.
The salient features are as follows: (1) In each study the slope for cigarette
smokers is smaller than the slope for non-smokers; (2) Within the cigarette
smokers the slope tends to decline, with some inconsistencies, as the amounts
smoked become greater; (3) for cigar or pipe smokers the slopes are closer
to those for non-smokers.

TaBLE 7.—IJncrease in natural logarithm of death rate per 1,000 man-years
for each 5-year increase in age, 6 prospective studies

 

 

 

 

 

 

|
British Men in 9 U.S. California | California ' Men in 25
Type of smoking doctors States veterans occupa- Legion ! States ?
tional |
. 593 474 .499 - 489 - 502 - 490
492 427 - 448 436 . 476 - 4388
- 536 . 484 - 490 401 . 567 ~ 445
. 551 - 457 ~ 454 - 461 ATL - 441
-477 - 420 - 467 447 - 449 401
. 401 845 |__----2- 2 |e |e -401
Cigars. ___ 2-22-22 222 2... . 466 +483 |---| ee 457
Pipes 200000 277222772 } - 698 { ‘521 1458 |i... -s |... sess ‘458

 

 

 

 

 

 

! “Cigarettes” includes “cigarettes and other” and current and ex-smokers.
2 First 10 months’ experience.

AGE AT WHICH SMOKING was STARTED

The study of U.S. veterans and the study of men in 25 states provide data
on the death rates of current smokers of cigarettes only, classified by the
age at which the person started to smoke. Since in both studies the men
who start to smoke early tend to smoke greater amounts per day than men
who start later in life, the mortality ratios to non-smokers are presented
separately for different amounts of smoking (Table 8).

TaBLE 8.—Mortality ratios by age at which smoking was started and by
amount smoked for current smokers of cigarettes only

 

 

 

 

 

Number of cigarettes per day
Age started to smoke Over-all
Tatio
1-9 10-20 21-39 40+
U.S. veterans:
Under 20__ 2... 22 222--ee eee enn 1.60 1.89 2.16 2.45 1,98
20-24 1,40 1.72 1.87 2. 23 1,72
115 1. 50 1. 1.11 1,39
1.79 12.23 22.21 2.15 2.17
1,75 11.83 22.01 2. 38 1.99
1.25 14,62 21.62 1.93 1. 58
1.03 11.36 21,45 1.56 1.34

 

 

 

i 10-19 cigarettes per day.
9 cigarettes per day.

89
For a fixed amount of smoking, the mortality ratios (with one exception)
exhibit a consistent and rather striking increase as the age at which smoking
was started decreases. This increase appears in all smoking groups of
Table 8. For men who started smoking cigarettes under the age of 20,
the over-all death rate was about twice that for non-smokers, whereas for
those who did not start until they were over 25 the death rate was only about
35 percent higher.

Mortatity Ratios By DuraTION OF SMOKING

Three studies have some data available on the number of years during
which the subjects had smoked. The comparison of mortality ratios for
different lengths of time smoked is of interest in relation to two questions
raised by Dorn (6) in an earlier analysis of the U.S. veterans’ data. Is there
a minimum period of use during which no effect on the death rate is notice.
able? Is there a maximum period after which no increase in the relative
death rate is perceptible?

For current cigarette smokers the results (Table 9) are not clear-cut. In
the U.S. veterans study, men smoking for less than 15 years had death rates
about the same as non-smokers. There is a rise of about 50 percent in the
mortality ratio for those who had smoked 15-35 years, with a further rise
for those smoking longer than 35 years. The study of men in nine states
shows a rise from under 25 years to 25-34 years duration, but no further
rise thereafter. In the Canadian study the mortality ratio with cigarette
smokers is just as high for durations less than 15 years as for durations of
15-29 years, though there is a rise (to 1.73) for smokers of cigarettes only
who have been smoking more than 30 years.

TABLE 9.—Mortality ratios for current smokers by type of smoking and by
length of time smoked

 

Number of years smoked

 

 

 

 

 

Type of smoking U.S. veterans Canadian veterans Men in 9 States
<15 | 15-24 | 25-34 | 354 <15 | 15-29 | 304 <25 | 25-34 | 35+
|
Cigarettes only._... 0.92 | 1.52 1.50 1.88 152) 144 1.73 1.46 1,74 1.78
Cigarettes and :
other. _..---2---- 107; 1.41 1.33 1.49 1, 24 1.27 1.22
Cigars only .._.... 0.92 | 0.94 0.95 1.12 1,06 0.81 1.31
Pipes only. ._--.__- 1.01 1,34 0.97 1.07 1.36 0, 93 1.09

 

 

Thus, all three studies show some increase in the mortality ratios with
longer duration of smoking, but the pattern is irregular. In a further break-
down of the data by amount smoked, Hammond and Horn (10) found no
trend with duration for men smoking more than a pack a day, but the other
two studies show an upward trend for this group of smokers.

For cigar smokers the only groups showing an increase in death rates over
non-smokers are those smoking for the longest period (Table 9). The in-
creases of 12 percent for the 35 years or over group in the U.S. study and of

90
31 percent for the 30 years or over group in the Canadian study are both
statistically significant.

For pipe smokers no trend with duration of smoking is discernible. The
two figures which stand out (1.34 in the U.S. study and 1.36 in the Canadian
study) are both based on relatively small numbers of deaths.

INHALATION OF SMOKE

In two of the studies the subjects were questioned as to whether they
inhaled. In the study of men in 25 states each subject was asked to place
himself in one of the four classes: do not inhale, inhale slightly, inhale
moderately, inhale deeply. In the Canadian veterans study the subject simply
classified himself as an inhaler or non-inhaler.

For current smokers of cigarettes only in the U.S. study, 6 percent of the
subjects stated that they did not inhale, 14 percent inhaled slightly, 56 percent
moderately and 24 percent deeply. In the Canadian study 11 percent
classified themselves as non-inhalers.

Since inhalation practices may vary with the amount smoked, the results
for cigarette smokers (Table 10) are given separately for different amounts.
For the men in 25 states an increase in the degree of inhaling for a fixed
amount of smoking is in general accompanied by an increase in the mortality
ratio. The relation of inhalation to mortality appears quite marked: for
instance, non-inhalers who smoke 20-39 cigarettes daily have mortality
ratios no higher than moderate or deep inhalers who smoke 1-9 cigarettes
daily. With the very heavy smokers (40+) the figures in Table 10 suggest
that the mortality ratio may remain the same for non-, slight, and moderate
inhalers. The ratios of 2.05 (non-) and 1.97 (slight) are, however, based
on only 26 and 41 deaths, respectively.

TABLE 10.—Mortality ratios for smokers of cigarettes only by inhalation
status and amount of smoking

 

 

 

 

 

 

 

 

Cigarettes per day
Degree of inhalation Over-all
ratio
1-9 | 10-19 20-39 | 40+

Men in 25 States: |
None... 1.29 1.46 1. 56 2.05 1,49
Slight __ ~~ ae 1.29 1.68 1.84 1.97 1.68
Moderate. 1.61 1.82 1.84 2.01 1,83
Cann oP-n2----22eseneeene sn reeeeeneee, 1.88 1.76 2.18 2.50 2.20

‘anadian veterans: !

None. 1.05 2111 $1.08 [2 1.08
Ome...” 1.35 21.50 PLL foe 1, 52

 

: Aniounts are lifetime maximum amounts smoked.
; 10-20 cigarettes per day.
Over 20 cigarettes per day,

Looking along the rows of the U.S. veterans study it will be seen that for
tach degree of inhalation the mortality ratio increases with the amount
Smoked. Ipsen and Pfaelzer (14) have shown that the logarithms of the 16
death rates at age 6] (approximately the average age) can be adequately rep-

91
resented as an additive function of the amount of smoking and the degree of
inhalation (although other types of mathematical relationship would also ft
the data). In their analysis, the average change in logarithm of death rate
from “no inhalation” to “deep inhalation” is as great as the difference be.
tween consumption of less than 10 cigarettes and consumption of more than
40 cigarettes daily.

In the Canadian data the inhalers have higher mortality ratios than the
non-inhalers for each amount of smoking. No trend with amount of smok.
ing appears for the non-inhalers, but the ratios in this row are based on
rather small numbers of deaths.

For cigar smokers (current and ex-smokers) in the 25-state study 19 per.
cent stated that they inhaled to some extent. The mortality ratio is 0.89 for
non-inhalers and 1.37 for inhalers. The latter increase of 37 percent (based
on 91 deaths) is statistically significant, but as the data have not been sub.
classified by amount of smoking the result may be partially a reflection of
the increase in death rates noted in Table 4 for heavy cigar smokers. In the
Canadian study, 13 percent of the cigar smokers classified themselves as in.
halers, but the number of deaths is insufficient to present a breakdown of the
mortality ratio by inhalation status.

Among the pipe smokers there were 28 percent who inhaled in the US.
study and 18 percent in the Canadian study. The U.S. mortality ratios are
0.8 for non-inhalers and 1.0 for inhalers; the Canadian data contain too few
deaths to allow a breakdown by inhalation.

Ex-CIGARETTE SMOKERS

For men who had stopped smoking prior to the date of enrollment, Table
11 gives the mortality ratios from five studies for “cigarette only” smokers
and “cigarette and other” smokers. The corresponding results for current
cigarette smokers (from Table 2) are given for comparison. The distinc.
tion between current and ex-smokers is not of course clear cut, since some
current smokers may have stopped after enrolling in the study and some ex-
smokers may have later resumed smoking.

With one exception, the mortality ratios for ex-smokers lie consistently be-
low those for current smokers and above those for non-smokers. In inter-
preting comparisons of ex-smokers and current smokers there are at least
three relevant factors. If smoking is injurious to health, cessation of smok.
ing would be expected to reduce the mortality ratio. Secondly, some men
stop smoking because of illness. In the 25-State study, over 60 percent of
the men who had stopped smoking within a year prior to entry stated that a
disease or physical complaint was one of the reasons for stopping (12).
This factor would tend to make mortality ratios for ex-smokers higher than
those for current smokers. Finally, ex-smokers may have previously smoked
smaller amounts than current smokers. This factor is not the explanation
of the drops in mortality ratios in Table 11. In a further breakdown by
amount of smoking, made for the three largest studies, the mortality ratio
for ex-smokers is consistently below that for current smokers for each amount
smoked.

92
TaBLeE 11.—Mortality ratios for ex-smokers and current smokers of cigarettes

 

 

 

British Men in 9 U.S. Canadian ; Men in 25

doctors States veterans veterans States
Ex-cigarettes......---.--.----------------- 1.04 1.40 | 141 1,42 1. 50
Current cigarettes .-___._...----.----------- 1.44 1.70 1.79 1.65 1.83
Ex-cigarettes and other.-...--------------- 4.21 1, 29 1.21 1.18 1.81
Current cigarettes and other__-_.---------- 1.05 1.45 1.46 1.23 1.54

 

 

 

 

 

 

TaBLE 12.—Mortality ratios for ex-smokers of cigarettes only by number of
years since smoking was stopped and by amount smoked

 

 

 

 

Number of years stopped
Study Cigarettes Current
per day smokers
<i 14 1-9 5-9 104+
: <19 2.04 |.--------- 1,30 |_--.------ 1.08 1.61
Men in 9 States !...-.---..- { Se 2.69 |.--2.20-, 1.82 [7 1.50 2.02
i

. <19 1.60 1.62 j._-------- 1.46 0.81 1.73
Men in 25 States. .....----- { + 2. 80 201 |. 1.51 1.22 2.01

 

 

 

 

 

 

 

1 These data are from Hammond and Horn, 1958.

TaBLE 13.—Moritality ratios for ex-cigarette smokers by number of years of
smoking, U.S. veterans study

 

Number of years of smoking
Cigarettes per day

 

 

<5 15-24 25-34 35+
1-0. een eee cee eee 1.05 1.08 1.25 1,58
2p nnn 1.12 1.18 1.41 2.00

 

Age at which smoking was stopped

 

 

<45 45-54 55+
1.09 1) 1.51 |-_.
1.12 1.59 1,86 [-_..

   

 

 

 

 

 

Some supplementary analyses throw a little further light on this topic.
In the two American Cancer Society studies (Table 12) a breakdown is
given by the number of years since smoking was stopped.

Except for the smokers of under one pack a day in the 25-State study,
the mortality ratio for men who had stopped less than a year is higher than
that for current smokers. Thereafter the ratio drops steadily as the interval
since smoking was stopped increases.

In the U.S. veterans study, further breakdowns are available by the
numbers of years during which the ex-smokers were smoking and by the
age at which smoking was stopped (Table 13), as well as by the amount
of smoking. The mortality ratios are about the same for those smoking
less than 15 years as for those smoking 15-24 years. Thereafter the ratios
rise with longer durations of smoking. Table 13 also shows that mortality
ratios were higher for those who stopped smoking at later ages.

93
Ex-CicaRk AND PIPE SMOKERS

Mortality ratios for smokers of cigars only and pipes only who had
stopped smoking prior to the date of entry are given in Table 14, the cor.
responding ratios for current smokers being included for comparison.

For ex-cigar smokers the mortality ratios are higher than those for non.
smokers and higher than those for current smokers in all four studies pre.
sented. The same is true for ex-pipe smokers with the exception of the
Canadian study.

The interpretation of this result is not clear to us. According to Ham.
mond and Horn (10) and Dorn (6), the explanation may be that a sub.
stantial number of cigar and pipe smokers give up because they become ill:
some data from cigarette smokers that support this explanation have re.
cently been analyzed by Hammond (12). Further analysis of the US,
veterans data indicates that mortality ratios run highest in ex-smokers who
smoked heavily and for a long time.

TaBLe 14.—Mortality ratios for ex-smokers of cigars only and pipes only
and for current cigar and pipe smokers

 

 

 

Type of smoker British Men in U.S. Canadian Men in

doctors 9 States veterans veterans 25 States
Ex-cigar__-...._-_-----------2 2-22 - ee ee |e 1.65 1.30 1.17 1.%
Current cigar. _----..-------.--.----------[------ eee 1.10 1.07 1 0.97
Ex-pipe---.------2-- 2-22 ee 1.12 1.29 1.38 1.01 1B
Current pipe. .......-..2..22.22----2------ 10.95 1.05 1.06 1.10 0. 86

 

 

 

 

 

 

1 Pipe and cigar combined.

EVALUATION OF SOURCES OF DATA

THE Stupy PoPpuLaTIons

Various reasons dictated the particular choices made of the seven study
populations, considerations of feasibility playing an important role. None
of the populations was designed, in particular, to be representative of the
U.S. male population. Any answer to the question “to what general popula-
tions of men can the results be applied?”, must involve an element of un-
verifiable judgment. However, three of the studies have populations with
widespread geographic distribution within the United States, as do the
British and Canadian studies within their respective countries. Taken as a
whole, the seven populations offer a substantial breadth of sampling of the
type of men and environmental exposures to be found in North America and
Britain, as well as providing some variation in methodological approach,
although the basic plan was similar in all studies.

The seven studies differ considerably in size. They vary also in the extent
to which they are free from methodological weakness. The studies of men
in nine states and men in 25 States, for instance, suffer from the difficulties

94,
that the populations studied are hard to define, that the smokers and non-
smokers were recruited by a large number of volunteer workers, and that
completeness in the reporting of deaths was hard to achieve, since this de-
pends on reports from the volunteers. On the other hand these studies have
the advantage of being large and of having a broad geographic representa-
tion of the U.S. male population, while the second study is the only one that
attempts to investigate many other relevant variables in which smokers and
non-smokers may differ. In the California occupational study the focus of
interest is occupational differences in lung cancer mortality, smoking history
being recorded primarily in order to be able to adjust comparisons among
different occupational groups for differences in amount smoked. In the
analysis we have not attempted to rate the studies as to over-all quality or to
assign differential weights to their results, except that in the smaller studies it is
recognized that mortality ratios are subject to larger sampling errors. Our
attitude is to attach importance only to results that appear to be generally
confirmed by the studies.

Some idea of the relative death rates in these studies as compared with the
1960 white male population of the United States is given in Table 15, which
shows the age-adjusted death rates for ages 35 and over, using the age dis-
tribution of the U.S. white male population as a standard. (The choice of
1960 for the comparison is arbitrary, but the white male rate changed little
between 1955 and 1960.)

In all studies the death rates for non-smokers are markedly below those
of U.S. white males in 1960. Even the smokers of one pack of cigarettes or
more daily have death rates that average slightly below the U.S. white male
figure. To some extent this is to be expected, since hospitalized and other
seriously ill persons are not recruited in such studies. The sizes of the differ-
ences appear, however, surprising for the studies with United States popula-
tions. Hammond and Horn (10), in a special investigation on this ques-
tion, concluded that the discrepancy in their study was due to the screening
out of sick persons in recruiting plus probably a selection towards men of
higher economic levels. They point out that their death rates are substantially
above those for males who had held ordinary life insurance policies for from

TaBLE 15.—Age-adjusted death rates per 1,000 man-years for current
smokers of cigarettes only (aged 35 and over), by amount smoked, in seven
studies and for U.S. white males

 

 

  

Current smokers of
cigarettes only

Study Non- | US. white
smokers Males, 1960

Less than 1 pack

1 pack or more
British doctors..._.......--.-.-----22----eee--2e-eneee- 15.8 19.2 23.2 22.9

“S. veterans. _.__...__ 0 . . ,

California occupational 110.5 114.2 118.0 122.6
Galfornia legion ._- 11.3 16. 4 16.3 22.9
adian veterans_ - 14.1 22.1 24.2 22.9
Men in 25 States - 212.8 218.5 219.2 22.9

 

 

 

| Ages 50-69,

__? These figures may be too low by about 1.7 percent, since the person-years used in the computation
included some contribution by men who had not been fully traced.

714-422 O-64—8 95
5 to 15 years. The U.S. veterans’ study population also came mainly from the
middle and upper socio-economic classes (6).

Another reason might be a failure to trace all deaths. In mass studies
it is almost impossible to devise infallible provisions for recording every
death. The study directors were, however, experienced in handling this
problem and it seems unlikely that more than, say, 5 percent of the deaths
would be missed. (Moreover, in the studies of veterans it is to the family’s
advantage to report the death.)

Another contribution probably came from the failure to obtain data for
some members of the population. Evidence on this point is available from
the British doctors and the U.S. veterans’ studies, in which death rates for
the complete population (respondents and non-respondents) are available,
In these studies the death rate for the whole population exceeded that in
the respondents, but by only 5 percent to 10 percent, so that non-response
appears unlikely to be a major cause of the discrepancy.

So far as interpretation of results is concerned, the discrepancy raises
two points. It is clear that the seven prospective studies involve popula.
tions which are healthier than U.S. males as a whole. Secondly, the low
death rates for non-smokers suggest the possibility that the studies recruited
unusually healthy groups of non-smokers. In the case of the five studies
which had clearly defined populations, this selection would arise only if
the non-smokers who refused to enter the study had death rates much
higher than those who were enrolled. This point is discussed in the next
section.

Non-RESPONSE Bias

In all five studies that had a clearly defined target population, sizeable pro-
portions of the population were omitted. The major reason was failure to
answer the questionnaire; in addition, certain replies were rejected as too
incomplete. The percentages of the populations for which usable replies
were obtained were approximately as shown in Table 16.

TABLE 16.—Percentages of usable replies in five studies

 

 

 

 

 

 

British US, California | California | Canadian
doctors veterans occupa- Legion veterans
tional
68 | 68, 85 | 85 | 56 | 57

 

In the U.S. veterans study, 68 percent replies were obtained from the
1954 questionnaire. A second questionnaire, sent in 1957, enrolled an addi-
tional 17 percent, for whom data are available during the period 1957-60.
In the two American Cancer Society studies it is not possible to present
meaningful percentages, since each research volunteer selected her own
small part of the study population from among her acquaintances.

The possible effects of these amounts of non-response on the mortality
ratios have received little discussion. Some pieces of information about

96
non-respondents are available in two studies. From a recent sample, Doll
(4) states that (a) the death rate of non-respondents in the British doctors
study is higher than that of respondents; (b) consequently the death rate
for respondents is lower than that of British doctors as a whole, perhaps
by as much as 5 percent to 10 percent; (c) there are relatively more smokers
among the non-respondents than among the respondents. In the U.S. vet-
erans’ study, the death rate for the whole study population exceeded that for
the original 68 percent responders by 7 percent in 1958 and 5 percent in
1959. From this study one can also calculate mortality ratios separately,
during 1957-60, for the 1954 respondents and the 1957 respondents. The

results for smokers of cigarettes are as follows:

1954 1957 Non-
respondents respondents respondents
(68 percent) (17 percent) (15 percent)

Current cigarettes only_____________ 1.87 1.71 ?
Current cigarettes and other________ 1.56 1.33 ?

Those who did not respond in 1954 but did respond in 1957 show lower
mortality ratios than the original set of men giving usable replies. By
making guesses about the mortality ratios in the 15 percent of non-responders,
one can compare the resulting mortality ratio in the whole population with
that found in the original 68 percent. To consider how much of an over-
estimate the ratios of 1.87 and 1.56 might be, we might suppose, to illustrate
the method, that the mortality ratio is unity for the non-respondents. The
mortality ratio for the whole population then turns out to be 1.71 for cig-
arettes only and 1.44 for cigarettes and other. Thus, with a non-response
tate of 30 percent, the computed mortality ratio might overestimate by 0.1
or 0.2.

Berkson (1) produced a set of assumptions under which, with a mortality
ratio of 1 in the whole population and a response rate of 71 percent, the
mortality ratio in the respondents is found to be 1.5. Non-respondents are
assumed to be of two types. One group, destined to have a high death rate,
refuses because they don’t feel well. This group has a high refusal rate
(50 percent) for both smokers and non-smokers, since the reason for refusal
is illness and not smoking. In the remainder of the non-respondents, the
refusal rate is higher among smokers than non-smokers. Qualitatively,
these assumptions are not unreasonable and agree in direction with the
Tesults quoted previously for the British doctors and U.S. veterans’ studies,
Korteweg (15) worked further examples of Berkson’s model as applied to
individual causes of death in the first report of the study of men in nine
States. He concluded that the response bias in the mortality ratio might be
as high as 0.3. Both Berkson and Korteweg, had, of course, to make some
arbitrary assumptions about the sizes of biases from different sources,

Further discussion of the non-response bias and computations as to its
Magnitude are given in Appendix I. The computations indicate that re-
Ported mortality ratios lying between 1 and 2 might overestimate by as
much as 0.3, a mortality ratio of 5.0 might overestimate by 1.0, and one of
10.0 might overestimate by 3.0. Thus, under assumptions that are rather
extreme, although consistent with the available data about non-respondents,

97
the mortality ratios of cigarette smokers would still remain substantially
higher than unity after adjustments for these amounts of over-estimation,

MEASUREMENT OF SMOKING History

Measurement of the type and amount of smoking, being based on a single
mail questionnaire, was admittedly crude. Consider men recorded as cyr.
rent smokers of cigarettes only, Subsequent to enrollment, some of these
presumably stopped smoking, at least temporarily, and some took up other
forms, with or without cigarettes.

Similarly, some men recorded as non-smokers may have begun to smoke
cigarettes subsequently. Consequently, the group designated as “current
smokers of cigarettes only” presumably contained men who were, for some
period of time “ex-smokers” or “cigarette and other” smokers, while men
designated as “non-smokers” contained some who smoked cigarettes for a
time. It seems likely that this dilution of the contrast between the two
groups would make the mortality ratio of cigarette smokers, as reported in
previous tables, underestimate the mortality ratio of unchanging cigarette
smokers relative to unchanging non-smokers, particularly when we note
that the groups labeled “ex-smokers of cigarettes” and “cigarette and other”
smokers both had mortality ratios lower than the group labeled “current
smokers of cigarettes only”.

As regards number of cigarettes per day, two types of errors of measure.
ment may occur. There will be “random” errors of measurement (some
men overestimate the amount and others underestimate it) that tend to
cancel out over all men in the study. The effect of such errors is that
the reported data underestimate the increase in the mortality ratio per
additional cigarette smoked daily, the computed increase being an estimate
of B/(1+h), where B is the true increase and h is the ratio of the variance
due to errors of measurement in the amount smoked to its total variance,
Yates (17). There may also, however, be systematic errors in reporting
the amount smoked. Heavy smokers may tend to underestimate the amount
smoked, If this happens, the reported increase in mortality ratio per
additional cigarette smoked will be an overestimate of the true increase,
although the upward trend of mortality ratio with increasing amount
smoked will remain.

On balance, we are inclined to agree with the opinion expressed by the
authors of several of the studies to the effect that the general result of errors
in reporting smoking history is to depress the mortality ratios of smokers
relative to non-smokers, so that reported ratios will tend to be underestimates
so far as this source of error is concerned.

STABILITY OF THE Mortatity Ratio

The sampling distribution of the mortality ratio has not to our knowledge
been at all thoroughly investigated and appears to be complicated. As a
rough approximation (Appendix II), the ratio of smoker deaths to smoker

98
plus non-smoker deaths may be regarded as a binomial proportion with
mean AR/(1+AR) where R is the true mortality ratio, 4 is the ratio of the
expected smoker deaths to the observed non-smoker deaths and the sample
size is the number of smoker plus non-smoker deaths. From this approxima-
tion, confidence limits for R may be derived. This approximation requires
that (1) the age distributions of smokers and non-smokers do not differ
greatly and (2) all age-specific death rates are small. An alternative normal
approximation that avoids assumption (1) is also given in Appendix II.

The sampling variation of the estimate of R is seldom of major import
in this part of the report, since the ratios for total mortality are mostly based
on relatively large numbers of deaths. The estimate has a positive mathe-
matical bias, negligible with large but not with small numbers of deaths.
In another sense the particular mortality ratio used in this report has a
different kind of bias. Since the standard age-distribution used in this
ratio is the age-distribution of the smokers, who are somewhat younger than
the non-smokers, the mortality ratios apply to populations slightly younger
than the combined population of the study. This is not in our opinion a seri-
ous objection, but may sometimes be relevant in questions of interpretation.

OTHER VARIABLES RELATED TO DEATH RATES

As mentioned previously, the smokers and non-smokers in these studies
may differ with respect to other variables that might influence the death rate.
Except in the new 25-State study, no attempt was made to measure these
variables apart from urban-rural residence, and previous reports on these
studies give little discussion of this problem. For urban-rural residence, Doll
and Hill (5) found that the proportions of smokers of different amounts
in the study population were about the same in rural areas, small cities and
large cities. In three studies the mortality ratios of cigarette smokers were
computed separately by size of city (6, 10, 11). In the study of men in
25 States, the data refer to men who smoked 20 or more cigarettes a day
and said that they inhaled moderately or deeply. In all three studies the
mortality ratios show little change with size of community (Table 17).

In the 25-State study, over 20 other variables that may be associated with
death rates were recorded. The study population was broken down into
subgroups for many of these variables separately: for instance, into smokers
who have long-lived parents and grandparents and those whose parents and

TaBLe 17.—Mortality ratios for cigarette smokers by population-size of city

 

Population-size

 

 

 

 

 

 

 

Study i
Over 10,000- Small Rural
50,000 | 50,000 towns
Men in 9 States 1.48 1.62 1,50 1,52
-S. veterans. ______- 1.54 1.51 1,42 1.59
Men in 25 States 1.89 12,02 1.74

 

 

‘Includes towns of less than 10,000.
grandparents were short-lived. Included among these variables were relj.
gion, educational level, native or foreign birth, residence by size of town
and occupational exposure, use of alcohol, use of fried food, amount of
nervous tension, use of tranquilizers, and presence or absence of prior
serious disease. For cigarette smokers who smoked more than a pack a day
and inhaled moderately or deeply, the mortality ratio was computed within
each subgroup. For example, the mortality ratio was 1.99 for men with
long-lived parents and 2.30 for men with short-lived parents. In every
subgroup the mortality ratio was well above unity, the lowest among 7]
computed ratios being 1.57 (for men with a history of previous serious
disease).

These data provide information on the association of the other variables
with mortality as well as on the association of smoking with mortality. Foy
six of the most relevant variables, Table 18 gives age-adjusted death rates,
using the combined populations of non-smokers and cigarette smokers ag
the standard population. The death rates apply to a period of roughly
22-months follow-up. As already mentioned, the cigarette smokers (of
more than a pack per day who inhaled moderately or deeply) have higher
death rates than the non-smokers in every cell of Table 18. Since not all
respondents answered these supplementary questions, the results may be
subject to some additional non-response bias.

As would be expected, death rates are relatively high for men with previ.
ous serious disease and for men from short-lived families, and are somewhat

TaBLE 18,—Age-adjusted death rates per 1,000 men (over approximately
22 months) for variables that may be related to mortality

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Long-lived Short-lived No previous Previous
Type of smoking parents and parents and serious serious
grandparents | grandparents disease disease
None..._- 14.8 21.1 1L5 42.5
Cigarettes 27.1 44.8 22.3 5.0
Single Married Use tran- Do not use
quilizers tranquilizers
None.... 26.0 18.9 29.1 18.2
Cigarettes 50.1 33.0 52.4 31.8
Educational level
|
No high . Some high |High school Some College
schoo} | school graduate college graduate
None... 222022222222 oe eee eee ence 22.7 | 20.0 16.9 18.3 15.8
Cigarettes}. 2222222222222 eee eee 35. 2 | 34.5 35. 5 34.2 29.4
Degree of exercise 2
None Slight Moderate Heavy
None.__....--2-------2-------- 2-2 ee eee 23.8 14.7 11.0 25
Cigarettes }_._..___.___--2- 22-2222 2 34.1 25.5 20.8 19.7

 

 

 

 

 

' Smokers of more than a pack per day who inhaled moderately or deeply. .
2 Confined to men with no history of heart disease, stroke, high blood pressure or cancer (except skin)

who were not sick at the time of entry.

100