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Association 131(3): 205-209, May 1946.

WEISS, N.S. Cigarette smoking and arteriosclerosis obliterans: An epidemiolog-
ic approach. American J ournal of Epidemiology 95(1): 17-25, 1972.

WESSLER, S., MING, S.-C., GUREWICH, V., FREIMAN, D.G. A critical
evaluation of thromboangiitis obliterans. The case against Buerger’s disease.
New England Journal of Medicine 262(23): 1150-1160, June 9, 1960.

WILHELMSEN, L. Recent studies on smoking and CVD epidemiology:
Scandinavia and some other Western European countries. In: Steinfeld, J.,
Griffiths, W., Ball, K., Taylor, R.M. (Editors). Proceedings of the Third World
Conference on Smoking and Health, New York, June 2-5, 1975. Volume II.
Health Consequences, Education, Cessation Activities and Social Action. U.S.
Department of Health, Education, and Welfare, Public Health Service,
National Institutes of Health, National Cancer Institute, DHEW Publication
No. (NIH) 77-1418, 1977, pp. 171-17.

WISSLER, R.W., VESSELINOVITCH, D., GETZ, G.S. Abnormalities of the
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(156) WOLINSKY, H. A new look at atherosclerosis. Cardiovascular Medicine: 41-54,

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(157) WRAY, R., DEPA.

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bypass grafts: Influence of cigarette smoking. Surgery 70(6): 969-973,

December 1971.
5. CANCER.

 

National Cancer Institute
CONTENTS

 

 

 

Introduction ......cccccccccec eee ne nese ec et eee ce ne eee ee aeeeen eee nen en ees 9
Lung Cancer ...........ccccecseececeeseeee nese sn enec ana nen eterna eee eeaes 9
Trends in Lung Cancer Mortality............-..::0:seeee 10
Epidemiological Studies ...........:--:::s:seereeerrssreesesees 11
Dose-Response Relationships ..........--..-sssseeereeeneeeeees 12
Number of Cigarettes Smoked Per Day........... 12
Age at Which Smoking Began.............---..++-+++ 13
Inhalation of Cigarette Smoke...........-.--:::s0s00 14
Tar and Nicotine Content of Cigarettes ........... 15
Lung Cancer in Women ............::ssereceeeeneereet ene eees 16
Trends in Cigarette Consumption
among Females ............-:ceseseeesesereetneeenen eee 16
Epidemiological Studies..............:::::ssssseeeeeeeees 20
Dose-Response Relationships ..............-:+sseeeeeees 21
Patterns of Cigarette Use............--:cesecserereeees 21
TWINS ......ccccecee cee eca cece ec ecee eee ee enon eseene eee ee seen see eneeens 23
Lung Cancer and the Use of Other Forms
Of Tobacco .........cccececeeeceecee eee eeeeen ec eens neeeeseeeennes 23
Histology of Lung Cancer...............-:sssseeseecereneneees 23
Cessation of Smoking..............ccccssenseneeeeeeneeeeeeeeees 2A
Lung Cancer and Air Pollution..............:+::sseeereeeees 25
Lung Cancer and Occupational Factors.............--+++- 27
ASDeStOS......0ccccccecec cence ec eeneeeeeeeeen teen ee ee eeseeens 28
Uranium Mining............c.ccceceesceeeeeeeeeeeneeeeenes 28
Nickel..........cccceecececeececeeeeseeeeeseeeneeseaeeeneseeegs 28
Chloromethyl Ethers ...........::.::2eeeeeeseeeeeeeeeees 29
Animal Studies ..............2:ceceeeeeeee seen ene eneanenensen ens 29
Skin Painting and Subcutaneous Injections....... 29
Tracheobronchial Implantation and Instillation...29
Inhalation Carcinogenesis .............:esceeeeeeeeeeee es 30
NitroSAMiNeS...........cececee ee eee nent eeeeneeeeneesaneneees 30
Phagocytosis ..........::cccseeceeeseeseeeneeerereeeeneeeees 31
Conclusions..........0c0cececececesensecececenenensneseseneesteenes 31
Cancer of the Larynx ........:..c.cssseceeceeeeeneeeeeneeeeesenee ens 32
Epidemiological Studies ............::::ceseeeseeeeeeresseeeeens 33
Asbestos .....ccccccccceeseceeceseeceeeeececeeseuaeeseeeeeeenaane eres 34
Animal Studies ...........c.:cccecssceeeecer sneer eeeeeeu een enenes 34

53
 

 

 

 

 

 

Oral Cancer ......:ccseessessseeeececeneeeenaneeneeeeseneseseeeeeeeeee ees 39
Epidemiological Studies ...........---sersreesrsrrsererereeys 39
Other Forms of Tobacco..........:cscsreecreesrserseeeneeneees 40
Other Risk Factors ...........::sseesecerssceesreeeneeennaeenenss 40
Leukoplakia.........sssccccsseecsssessrsnssesececntereeeeees seen 41
Animal Studies ...........ccsecceseseeeereneeenereseaesseneeeoenss 41
Conclusions..........:cccscccesseceeeeee essa escusnceeaescanesseee ss 42

Cancer of the Esophagus............::sccereseseereeesnrnrreeenetes 42
Epidemiological Studies .......-..:::-ssssecccrreseereeeereseees 42
Other Forms of Tobacco Use ...........-ssserseeesrersteenes 43
Other Risk Factors .........cc:sscceeecsseeerseseeenseeeneseusees 43
Autopsy Studies ........-:sscccceesrssreeeeeseeeseneeesessenes 44
Animal Studies ...........:::ccccrseesceeeeeeneneneceranasennenees 44
Conclusions.........-:2seceeeeeeeeneeeeeeneesennanseseneeseeeeeesees 44

Cancer of the Urinary Bladder and Kidney............------+ 45
Bladder Cancer .........scceeceseeecneneseseneccrteescneeneaeoees 45

Epidemiological Studies.........--++-ssceeerseereeeees 45
Other Risk Factors ........:.:::ceeeeceseeesse reese eeenees 47
Animal Studies...........2::cceeeseeeeeneeeeeeeeesesseeees 47
Kidney Cancer ......:.::ccscsreccceree sevecesaeesereceeneeesenes 47
Epidemiological Data..........+s:::-ersssrrrerersrretees 47
Conclusions.........ccscccecceeeneeecneeeesnenenecsan arse eceeee nee 49

Cancer of the Pancreas...........scsccsssssresesserenenerrersenenees 50
Epidemiological Studies .......-...--:sessccreressersserere 50
Other Risk Factors ..........:::ccseeeeseeeereecressnesereeceeres 51
Animal Studies ...........ccescsseerecsecreeen rece eeesenenaenenees 51
Conclusions........cc.cceeeeceee ree ec nee e ee ee nee nee eee eee eee eee 53

Mechanisms of Carcinogenesis .........--+-sseersreeeeereeeeeseees 53
Smoke Composition...........:sssseceeeeereeeeeeee esas eerste: 53
Experimental Models..........-:ssccseessreseerertsrrsseteeers 53
Concepts of Carcinogenesis.............cscrrrrerereerreeereess 54
Aryl Hydrocarbon Hydroxylase ........-:csesseeeeeenseresees 57
Multi-Stage Model of Carcinogenesis.......-..0:ssesseeee 58

References .....ccccccccccecee eee eee e ene eee eee nen eee e teens eens eee es 59

5—4
LIST OF FIGURES

Figure 1.—Relative risk of lung cancer for males, by
number of cigarettes smoked per day and long-term use
of filter (F) and nonfilter (NF) cigarettes................-. 18

 

 

Figure 2.—Relative risk of lung cancer for females, by
number of cigarettes smoked per day and long-term use
of filter (F) and nonfilter (NF) cigarettes.................. 19

 

Figure 3.—Lung cancer mortality in continuing cigarette
smokers and nonsmokers as a percentage of the rate
among ex-cigarette smokers at the time they stopped
SMOKING .........0eccseseece eee eeeeceeeeaeseesanea eee eeeseneneeese eens 26

 

Figure 4.—Relative risk of developing larynx cancer for
males, by number of cigarettes smoked per day and use
of filter and nonfilter cigarettes............:::sceeseeeeeseeees 35

 

Figure 5.—Relative risk of developing larynx cancer for
females, by number of cigarettes smoked per day and
use of filter and nonfilter cigarettes ............:...:seeeeees 36

 

Figure 6.—Relative risk of developing larynx cancer for
male ex-smokers, by years of smoking cessation.......... 37

 

Figure 7.—Relative risk of developing larynx cancer for
female ex-smokers, by years of smoking cessation ....... 38

 

Figure 8.—Relative risk of pancreatic cancer in males, by
number of cigarettes smoked .............cseseesesensereneeeees 52

LIST OF TABLES

Table 1.—Lung cancer mortality ratios—prospective

 

5—5
 

Table 2.—Lung cancer mortality ratios for males, by
current number of cigarettes smoked per day, from
selected prospective studies ........--s-scrsersersserrettrrsrr ss 13

 

Table 3.—Lung cancer mortality ratios for males, by age
began smoking, from selected prospective studies ........ 14

 

Table 4.—Lung cancer mortality ratios for males, by
degree of inhalation, from selected prospective
Studies. .....-seccccccccecceeseesereeeneseee ne eeeeee sega eeeeee esse genes 15

 

Table 5.—Age-adjusted lung cancer mortality ratios for
males and females, by tar and nicotine in cigarettes

 

Table 6.—Age-adjusted lung cancer mortality ratios for
males and females, comparing those who smoked a few
high T/N cigarettes with those who smoked many low
T/N cigarettes......cccccccccesseeceeeneer sete tte eee 17

 

Table 7.—Mortality rates for lung cancer and cancer of
the respiratory tract for white females in the United
States per 100,000 population for selected years: 1940 to

 

Table 8.—Percent of adult population who were current
cigarette smokers in selected years in the
United States ......c.ccceescccecceeeereeersrenesseseees sess neg se eee 20

 

Table 9.—Percent of teenagers who were current cigarette
smokers in selected years in the United States........... 21

 

Table 10.—Lung cancer mortality ratios for women—
prospective Studies.........+---srrsessseees seeteeeeseeeneeennnes 21

 

Table 11.—Lung cancer mortality ratios for females, by
number of cigarettes smoked per day: A.C.S. 25-State

 

Table 12.—Lung cancer mortality ratios for females, by
number of cigarettes smoked per day: Haenszel and
Taeuber ....ccccccceceeecceeeee eee eee eee eee rere EE EEE ee 22

 

Table 13.—Lung cancer mortality ratios for females, by
duration of smoking: Swedish Study .....cceeeeeeeeee eee eees 22

5—6
 

Table 14.—Lung cancer mortality ratios for females, by
degree of inhalation: A.C.S. 25-State Study.......0...00... 22

 

Table 15.—Lung cancer mortality ratios in ex-cigarette
smokers, by number of years stopped smoking............ 25

 

Table 16.—Mortality ratios for cancer of the larynx—
prospective studies...............cccceccccessecessauscseescuceecees 33

 

Table 17.—Mortality ratios for cancer of the oral cavity—
Prospective studies............. ce cecec cee sceseesessevevseeceeeeues 40

 

Table 18.—Mortality ratios for cancer of the esophagus—
prospective studies.................c.ccccccccsesceececeeacensevaeees 43

 

Table 19.—Bladder cancer mortality ratios—prospective
StUIOS..... 0... eee cece eeeeeneeceeeeeceeeneeeeuveceususssaueeeaness 46

 

Table 20.—Kidney cancer mortality, ratios and relative
risks: selected prospective and retrospective studies ..... 48

 

Table 21.—Kidney cancer mortality ratios, by amount
smoked: U. S. Veterans Study..............cccccccesceseeeeeees 49

 

Table 22.—Pancreatic cancer mortality ratios—prospective
StUdICS 0... cee cec ceca eee eseesneseccsscucesceuscueeeeenesenes 51

 

Table 23.—Mortality ratios for cancer of the pancreas
among Swedish subjects, aged 18-69, by sex and
amount smoked.............0..ccccecceeceeceecsecesensecuccsecuecaes 52

 

Table 24.—Carcinogenic, promoting, and ciliatoxic agents
in the gas phase of tobacco smoke.................csseeeseees 55

 

 

Table 25.—Carcinogenic agents in the particulate phase
Of tobacco smoke ..............ccceeccccccessseesceseseueeteceeees 56

 

Table 26.—Tumor promoters and co-carcinogens in the
particulate phage of tobacco smoke ...................000cc00e 57
Introduction

Cancer has been the second leading cause of death in the United States
since 1937. There were an estimated 390,000 deaths from cancer in 1978
(4). The association between tobaceo smoking and the development of
lung cancer was first suggested in the 1920’s and early 1930’s (159,
206). In the early 1950’s, more than a dozen retrospective studies were
published which first generally alerted the medical and scientific
community to the health hazards associated with cigarette smoking.
The public was informed of the results of these studies, and as a
consequence there was a significant, but brief, dip in the per capita
consumption of cigarettes. The next decade brought an intensive
worldwide investigation into the various diseases associated with
cigarette smoking. The first official statement on smoking and health
by the U.S. Government was contained in the Report of the Advisory
Committee to the Surgeon General of the U.S. Public Health Service,
which was released 15 years ago. The evidence available at that time
warranted the conclusion that “Cigarette smoking is causally related
to lung cancer in men; the magnitude of the effect of cigarette
smoking far outweighs all other factors. The data for women, though
less extensive, point in the same direction. The risk cf developing lung
cancer increases with the duration of smoking and the number of
cigarettes smoked per day, and is diminished by discontinuing
smoking” (217). In the 15 years since the 1964 Surgeon General’s
Report was published, these conclusions have been confirmed by
numerous investigations in many countries. Cigarette smoking has also
been implicated as a significant cause of cancer of the larynx, oral
cavity, esophagus, urinary bladder, kidney, and pancreas. As data
concerning the relationship of smoking to the development of cancer at
various sites became available, they were summarized and published in
the annual issues of the Health Consequences of Smoking (209, 210,
211, 212, 212a, 218, 214, 215, 216).

This chapter reviews the epidemiological and experimental data for
each of the cancer sites associated with cigarette smoking. Discussions
of the specifie cancers are presented sequentially, based on the
strength of the association with cigarette smoking: cancer of the lung,
larynx, oral cavity, esophagus, urinary bladder, kidney, and pancreas.

Lung Cancer

This year more people in the United States will die from lung cancer
than from any other malignant disease. In 1950, when the nation first

me generally aware that there was an association between
smoking and lung cancer, there were 18,318 lung cancer deaths. In
1964, there were 45,838 deaths from lung cancer. The National Center
for Health Statistics reported that in 1976 there were 86,267 deaths
from lung cancer in the United States (150). It is estimated that there

5—9
were 92,400 deaths from lung cancer in 1978 (4). For every preventable
death from highway accidents, there were approximately two deaths
from lung cancer which could have been prevented if the individual
had not smoked cigarettes. There are about 280 deaths from lung
cancer each day in the United States.

This epidemic increase in lung cancer is reflected in rapidly changing
mortality rates in both men and women. The mortality rate for men in
1950 was 19.9/100,000/year. This rose to 41.4 in 1964, and to 63.0 in
1976. The comparable figures for white females were 4.7 in 1950 and
8.0 in 1965, and climbing rapidly to 19.5 in 1976 (Table 7).

According to results from the National Cancer Institute’s Surveil-
lance, Epidemiology, and End Results (SEER) Program, the mortality
rates for black males and females are higher than for whites. In 1976,
the lung cancer mortality rate for black males was 93.0, for black
females it was 17.4 (154). Due to recent increases in death rates among
females, the ratio of male to female mortality for lung cancer has
dropped from 7:1 to less than 4:1.

While recent years have seen dramatic increases in relative survival
rates for acute leukemias in children, Hodgkin’s disease, multiple
myeloma, and certain other malignancies, there has been little increase
in survival rates for lung cancer. The 5-year survival rate for lung
cancer in all states is 8 percent for males and 12 percent for females
(151). The difference in survival rates between males and females can
be explained by sex-specific differences in histology or stage of the
disease.

Trends in Lung Cancer Mortality

In the United States there has been in the past few years a significant
reduction in the percent of males and females who smoke cigarettes.
As yet, there has not been a decline in the age-adjusted total mortality
rates for lung cancer. When the lung cancer mortality rates by age are
examined from 1950 through 1975, there is a continuining increase in
older age groups for both males and females. This is probably due to
the elevated risk experienced by older persons who use nonfiltered,
high tar and nicotine cigarettes and who have done so for the majority
of their lives. However, for female cohorts born in 1950-54 and male
cohorts born in 1935-39 and 1940-44, the age-specific lung cancer
mortality rates are below those of previous cohorts. This probably
results from the reductions in cigarette consumption which have
occurred in these groups.

There has been a change in the epidemic of lung cancer in England
and Wales, as summarized by the International Union Against Cancer
(UICC) workshop on the biology of cancer (243):

In England and Wales, lung cancer mortality stopped increasing in

men under the age of 50 years during the 1950’s and more recently

has fallen in men under the age of 60 years. The death rate from

5—10
lung cancer in women ages 40 years and over has continued to rise,
but has leveled, or fallen in younger women since the 1960’s...The fall
in lung cancer mortality among men under the age of 60 years is
likely to be due to their reduced consumption since the end of the
Second World War, and to the reduction in the tar yield of cigarettes
since 1955; particularly with the change to filter cigarettes.
Although lung cancer mortality in women over 40 years has
continued to increase along with their cigarette consumption, it is
unlikely that the incidence of lung cancer will ever reach the high
levels recorded in men, because the increasing cigarette consumption
by women has been, and is continuing to be compensated for by a
decrease in tar yield.

Epidemiological Studies

The first comprehensive reviews of the effects of smoking on lung
cancer were published in 1962 and 1964 by the Royal College of
Surgeons of London and the Surgeon General of the United States,
respectively (171, 217). They included data from studies on epidemiolo-
gy, profiles of the consumption of tobacco, the composition and
carcinogenicity of components of tobacco smoke, the effects of smoke
on experimental animals, and the pathological changes observed in
humans and animals. The conclusions reached in these assessments and
by all of the periodic reviews that have followed at regular intervals
(209, 210, 211, 212, 212a, 213, 214, 215, 216) are impressively uniform
and consistent. So much so that it has been observed that the results of
any one of the major studies might be taken to represent all of them.

There have been at least nine major prospective epidemiological
studies which have examined the relationship between cigarette
smoking and mortality from various causes. The results of eight of
these studies are related to cigarette smoking and lung cancer and are
presented in Table 1. The lowest mortality ratios are experienced by
female smokers. The mortality ratios for male cigarette smokers are as
low as 3.85 for Japanese males and as high as 14.0 for British doctors
and Canadian veterans. Combining the data from the largest studies
allows the conclusion that cigarette smokers on the average are 10
times as likely to develop lung cancer as nonsmokers. The mortality
ratios are much higher for heavy cigarette smokers. This will be
detailed in the section on dose-response relationships.

In the past 30 years, more than 50 retrospective studies on the
relationship between cigarette smoking and lung cancer have been
published. These data are too extensive for convenient summarization;
they have been reviewed in recent issues of the Health Consequences
of Smoking (272, 212a, 213, 214, 215).

5—11
TABLE 1.—Lung cancer mortality ratios—prospective studies

 

 

: . Number Cigarette
Population Size of deaths Nonsmokers smokers
British

doctors(47a) 34,000 males 441 1.00 14.0
Swedish 27,000 males 55 1.00 82

study($2) 28,000 females 8 1.00 45
Japanese 122,000 males 590 1.00 3.76

study(77a,78) 143,000 females 148 1.00 2.08
ACS. 25- 440,000 males 1,159 1.00 9.20

State Study(65) 562,000 females 188 1.00 2.20
U.S. veterans(90) 239,000 males 1,256 1.00 12.14
Canadian

veterans(20) 78,000 males 331 . 1.00 142
ACS. 9

State Study(68) 188,000 males 448 “1.00 10.73.
California males

in 9 occupa- :

tions(228) 68,000 males 368 1.00 761

 

Dose-Response Relationships ©

An important factor in the causal relationship between smoking and
lung cancer. is the demonstration of dose-response relationships. In
most epidemiological studies, dosage has been measured by the number
‘of cigarettes smoked per day at the time of entry into the study. Other
dose variables which have been examined include the maximum
number of cigarettes smoked per day, the age an individual began
smoking, the degree of inhalation of tobacco smoke, the total number
of years an individual has ‘smoked, the total lifetime number of
cigarettes smoked, tar and nicotine levels of the brand of cigarettes
used, the number of puffs per cigarette, the length of the unburned
portion of the cigarette, and combinations of these variables into
“dosage” scores. All of these variables have been shown in one study or
another to contribute to the risk of developing lung cancer. Only a few
representative samples of dosage variables as related to lung cancer
mortality are examined in this section. :

Number of Cigarettes Smoked Per Day

The risk of developing lung cancer increases with the number of
cigarettes smoked per day. In the U.S. and British populations, the risk
of developing lung cancer for individuals smoking more than two packs

5—12
TABLE 2.—Lung cancer mortality ratios for males, by current
number of cigarettes smoked per day, from selected
prospective studies

 

 

“roked Morality
ratio
per day
ACS. 25-
state study(65) Nonsmoker 1.00
1-9 4.62
10-19 8.62
20-39 14.69
40+ 18.77
British
doctors(47a) Nonsmoker 1.00
1-14 7.80
15-24 12.70
25+ 25.10
Swedish males(32) Nonsmoker 1.00
1-7 230
815 8.80
16+ 13.90
Japanese males(78) Nonsmoker 1.00
19 1.90
10-14 3.52
1-4 4.11
25-49 4.57
50+ 5.78

 

a day is approximately 20 times that of nonsmokers (47a, 65, 68, 80,
228). Data for Swedish males are of the same magnitude (32). Japanese
males who smoke 50 or more cigarettes a day experience a risk which is
5.8 times greater than for nonsmokers. Hirayama noted that the slope
of the dose-response curve for lung cancer was less in Japan than in
the United States and that this was probably due to the lower
percentage of regular deep inhalers, a lower level of environmental
promoting conditions, and also a higher percentage of adenocarcinoma
in Japan than in the United States (78). Table 2 presents lung cancer
mortality ratios from selected prospective studies for males by the
current number of cigarettes smoked per day.

Age at which Smoking Began

Lung cancer mortality ratios exhibit an inverse relationship with the
age of initiation of the smoking habit. Lung cancer mortality ratios for
males by age at which they began smoking are presented in Table 3.
Most cigarette smokers began the habit while in high school and are at
the greatest risk of developing lung cancer. Those who began smoking

5—13
TABLE 3.—Lung cancer mortality ratios for males, by age began
smoking, from selected prospective studies

Age began

 

. Mortality
smoking .
. ratio
in years
ACS. 25-
State Study(65) Nonsmoker 1.00
B+ 4.08
20-24 10.08
15-19 19.69
under 15 16.7
Japanese
study(78) Nonsmoker 1.00
25+ 2.87
20-24 3.85
under 20 4.44
US. Nonsmoker 1.00
veterans{ 90) 25+ 5.20
20-24 9.50
15-19 14.40
under 15 18.70

 

after the age of 25 have mortality ratios which are only 4 to 5 times
greater than those of nonsmokers.

Inhalation of Cigarette Smoke

Inhalation of tobacco smoke is an important dosage variable. Inhala-
tion of smoke well into the lungs is the major mechanism whereby lung
tissue is exposed to the carcinogens which ultimately produce lung
cancer. Techniques for quantitating the degree of tobacco smoke
inhalation have been developed using carboxyhemoglobin levels or end
expiratory carbon monoxide levels as an index of smoke inhalation.
These objective methods of measuring inhalation have not been
applied to studies of lung cancer mortality. In most investigations, the
smoker was asked to report subjectively on his own inhalation
practices. This is subject to considerable variation but is not as
inaccurate as might be presumed. Available data show a strong dose-
response relationship between self-reported inhalation of cigarette
smoke and lung cancer mortality. Representative figures from selected
prospective studies are presented in Table 4. These data suggest that
cigarette smokers may underestimate the degree to which they inhale
cigarette smoke. Those who report that they do not inhale cigarette
smoke experience lung cancer mortality ratios which are 4 to 8 times
greater than for nonsmokers. Deep inhalation results in mortality
ratios which are as high as 17 times greater than for nonsmokers.

5—14
TABLE 4.—Lung cancer mortality ratios for males, by degree of
inhalation, from selected prospective studies

 

 

Degree Mortality,
of .
inhalation ratio
ACS. 25-
State Study(65) Nonsmoker 1.00
None 8.00
Slight 8.92
Moderate 13.08
Deep 17.00
Swedish
males{32) Nonsmoker 1.00
None 3.70
Light inhalation 7.80
Deep inhalation 9.20

 

Tar and Nicotine Content of Cigarettes

The major constituents of cigarette smoke that cause lung cancer are
among the more than 2,000 different compounds found in cigarette
smoke, Cigarette filters, first introduced during the mid-1950’s, have
the effect of trapping tar. Data presented by Maxwell (736) show that,
in 1976, more than 600 billion cigarettes were smoked and that 88.4
percent of these were filtered. It has been known that the risk of
developing lung cancer increased with the tar and nicotine content of
cigarettes. Until recently, however, there has not been a great deal of
evidence that individuals who switch to lower tar and nicotine
cigarettes experience less lung cancer mortality (27). It has been
argued that, if the tar and nicotine content of tobacco were reduced,
individuals might increase the number of cigarettes smoked per day
and thereby abolish any benefit that might be gained. Alternatively,
those who switch to low tar and nicotine cigarettes might inhale the
smoke more deeply than smokers of high tar and nicotine cigarettes,
and thereby exposure to tar and nicotine might not be reduced. In a
large prospective study by Hammond, et al. (67), these tar and nicotine
relationships were examined with respect to lung cancer. The 897,825
men and women in 23 States were divided into 3 tar and nicotine
categories. The high tar and nicotine (T/N) category was defined as 2.0
to 2.7 mg of nicotine and 25.8 to 35.7 mg of tar. The medium T/N
category was defined as 1.2 to 1.9 mg of nicotine and 17.6 to 25.7 mg of
tar. The low T/N category included cigarettes containing less than 1.2
mg of nicotine and less than 17.6 mg of tar. A matched-group analysis,
Similar to age standardization, was utilized. Individuals in each group
Were alike with respect to age, race, number of cigarettes smoked per

ay, age when they began to smoke cigarettes, place of residence,

5—15
TABLE 5.—Age-adjusted lung cancer mortality ratios* for males
and females, by tar and nicotine in cigarettes

 

 

smoked
Males Females
High T/N 1.00 1.00
Medium T/N 0.95 0.79
Low T/N 081 0.60

 

*The mortality ratio for the category with highest risk was made 1.00 so that the relative reductions in risk with
the use of lower T/N cigarettes could be visualized.
SOURCE: Hammond, E.C. (67)

occupational exposure to dust fumes, chemicals, etc., education, prior
history of lung cancer, and prior history of heart disease. Results of
this analysis are presented in Table 5. The mortality ratio for the
category with the highest risk was made 1.0 so that the relative
reduction in risk with the use of lower T/N cigarettes could be
visualized. For males smoking the same number of cigarettes per day,
there appears to be a 20 percent reduction in risk of developing lung
cancer with the use of low T/N cigarettes. For females, there was a 40
percent reduction in the risk of developing lung cancer with the use of
low T/N cigarettes, keeping the number of cigarettes smoked per day
constant. The amount of tar and nicotine taken into the body per day
depends on the number of cigarettes smoked, as well as on the tar and
nicotine content of each cigarette. Hammond conducted a second
matched-group analysis comparing subjects who smoked 1 to 19 high
T/N cigarettes per day and those who smoked 20 to 39 low T/N
cigarettes per day. These results are presented in Table 6. The number
of cigarettes smoked per day was a relatively more important variable
than the tar and nicotine content of cigarettes. The mortality ratio was
1.6 for males and 2.1 for females who smoked 20 to 39 low T/N
cigarettes a day, compared to individuals who smoked only 1 to 19 high
T/N cigarettes per day.

Wynder and Stellman (253) conducted a large retrospective study of
1,034 white males and females with histologically proved cancer of the
lung and larynx. Relative risks were consistently lower among long-
term smokers of filter cigarettes, compared to smokers of nonfilter
cigarettes. These groups were standardized for number of cigarettes
smoked, duration of smoking, inhalation, and cigarette butt length.
These dose-response relationships are presented in Figures 1 and 2.

Lung Cancer in Women
Trends in Cigarette Consumption Among Females

In 1964, the Advisory Committee to the Surgeon General concluded
that cigarette smoking was causally related to cancer in men, and that

5—16
TABLE 6.—Age-adjusted lung cancer mortality ratios* for males
and females, comparing those who smoked a few
high T/N cigarettes with those who smoked many
low T/N cigarettes

 

 

1-19 high T/N 20-39 low T/N

cigarettes/day cigarettes/day
Males 1.00 1.6
Females 1.00 2.1

 

*The mortality ratio for the category with lowest risk was made 1.00 so the increase in risk with smoking more
cigarettes/day could be illustrated.
SOURCE: Hammond, E. C. (67)

“the data for women though less extensive, point in the same
direction” (217). Today, 15 years later, the lung cancer epidemic among
women is well established. Several investigators had predicted sharp
increases in lung cancer mortality among women. In 1966, Linden (118)
examined lung cancer mortality in California women and predicted:
“One can expect to see further increase in the number of lung cancer
deaths and the death rates as the increasing proportions of women who
smoke cigarettes reach the age when lung cancer is most likely to
occur.”

In 1964, lung cancer was the fifth leading cause of death from cancer
in women. It became the fourth leading cause in 1967 and moved to the
third leading cause of death from cancer in 1969, passing cancer of the
uterus. Projections for 1979 indicate that lung cancer is approaching
cancer of the colon and rectum as the second leading cause of death
from cancer in women. If present trends are not reversed, during the
next decade lung cancer will become the leading cause of death from
cancer in women, exceeding deaths from cancer of the breast.

In 1955, there were only 4,100 deaths from lung cancer in women. In
1976, the National Center for Health Statistics reported there were
20,455 deaths from lung cancer among females in the United States
(150); the American Cancer Society estimated that in 1978 this
increased to 21,900 deaths (4).

These increases are not due to increases in the population. Death
rates for lung cancer have been steadily rising in women, especially in
the past decade. The lung cancer mortality rate for white females in
1950 was 4.7 per 100,000; by 1976 this had risen to 19.5 per 100,000. This
18 more than a fourfold increase (Table 7).

The Surveillance, Epidemiology and End Results (SEER) Program
of the National Cancer Institute recently reported that the lung cancer
death rate for black females exceeded that of white females (16.8
blacks, 15.0 whites)(154). Data from this survey are collected from 10
Seographic areas in the United States and therefore do not represent

5—17
LUNG CANCER I. MALES

       
  
       
      

     
    
     
   
  

    
 
  

   

     
 
 
 

  
 
   
   
   
   
      
       
    
    
   
    
   
     
     
       
   
    

        

  
       
      
   
     
    
   
   
      
      
    
   
     
   
    

   
     
        
       
     
   
     
    
    
 

 

     

 

  
 

 

 

 

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CASES 126
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NON F NF F NF F NF F NF
SMOKER 1-10 11-20 31—40 4i+

NO. OF CIGARETTES SMOKED PER DAY

FIGURE 1.—Relative risk of lung cancer for males, by number of
cigarettes smoked per day and long-term use of filter (F) or nonfilter
(NF) cigarettes

SOURCE: Wynder, E.L. (253)
national trends per se. The lung cancer mortality rate (15.0 per 100,000)
among black females in the general U.S. population is equal to that of
whites.

Increases in lung cancer mortality among females cannot be
explained by exposure to occupational carcinogens. Increases in
cigarette consumption are responsible for these trends.

5—18
  
 
 

     
      
    
      
     
 
      
      
      
   

    

     
       
   
      
  
 

 
 

 

LUNG CANCER |. FEMALES
___ CASES
* CONTROLS
3
25 2,
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25 mn 29
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ra
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NON F NF F NF F NF F NE
SMOKER 1-10 11-20 21-30 31+

NO. OF CIGARETTES SMOKED PER DAY

FIGURE 2.—Relative risk of lung cancer for females, by number of
cigarettes smoked per day and long-term use of filter (F) and

nonfilter (NF) cigarettes
SOURCE: Wynder, E.L. (253)

The epidemic of lung cancer in women has lagged behind that in
men, primarily because of differences in patterns of cigarette smoking.
There are fewer women smoking than men, but the gap is narrowing.
Among teenagers in several age categories, girls are smoking more
than boys (155). Table 8 shows the percentage of the U.S. adult
population who are currently smoking cigarettes for selected years. In
1975, approximately 29 percent of adult females were smoking,
whereas 39 percent of adult males were smoking (155). It should also
be noted that, over the past decade, there has been a 2.6 percent

5—19