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IO1


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102


          CHAPTER 4
SMOKING CESSATION AND RESPIRATORY
          CANCERS


CONTENTS

LungCancer ....................................................... 107
Pathophysiologic Framework. ....................................... 107
  Smoking and Histopathology of the Airways  ......................... IOX
  OtherChanges  ................................................. 109
Smoking Cessation and Lung Cancer Risk  ............................. I IO
  Pattern of Changing Risk After Cessation ............................ I IO
  Effect of Antecedent Smoking History  .............................. 122
   Duration of Smoking .......................................... 122
   Daily Cigarette Consumption  ................................... I23
    Inhalation Practices  ........................................... 123
    Different Tobacco Products ..................................... I24
   Effect of Age at Cessation ...................................... I25
Multistage Modeling  .............................................. I26
Cessation After Developing Disease  .................................. I29
Cessation After Diagnosis of Lung Cancer ............................. I29

LaryngealCancer.. ................................................. I31
Pathophysiologic Framework ........................................ I3 I
Smoking Cessation and Laryngeal Cancer Risk  ......................... I3 I

Conclusions  .................. YT.rTTZTT. .................... I-. -135

References  ........................................................ 137


LUNG CANCER

Epidemiologic studies have provided overwhelming evidence for a causal association
of cigarette smoking with lung cancer (US PHS lY63: US DHEW 1979: US DHHS
1989). The plausibility of this association is supported by the presence of numerous
carcinogens in tobacco smoke. Compared with the risk among never smoker\. the risk
of lung cancer for smokers may be increased twentyfold or more for heavy smokers
(US DHHS 1989). Risk of lung cancer increases with the number of cigarettes smoked
daily and the duration of cigarette smoking; risk declines after cessation (US DHHS
1982, 1989). For example, in an analysis of data from the British Physicians Study.
Doll and Peto (1978) indicated that among sub.jects w,ho persisted in smoking. lung
cancer incidence increased with the fourth or fifth power of the duration of smoking
and with approximately the square of daily cigarette consumption. In 19X5. estimated
attributable risks of lung cancer from cigarette smoking were 90 percent for males and
79 percent for females in the United States (US DHHS 1989).

This Section considers the effects of cigarette making on the epithelium of the
airways of the lungs. the site from which most lung cancers stem. and the evolution of
the smoking-related change, after cessation. The epidemiologic evidence on lung
cancer risk after smoking cessation is comprehensively reviewed; the change in risk
over time following cessation is described; and factors modifying the effect of cessation
are considered. The Section includes discussion of the application of multistage
modeling to data on smoking cessation.

Pathophysiologic Framework

Previous Surgeon General's reports have provided extensive reviews on carcinogenic
components of tobacco smoke and on experimental carcinogenesis with tobacco smoke
(US DHEW 1979; US DHHS  I98 2. 1986). Tobacco smoke contains numerous
carcinogenic agents with both initiating and promoting activity. Although the specific
mechanisms of respiratory tract carcinogenesis by tobacco smoke are not yet fully
characterized, the plausibility of the smoking-lung cancer relation has been considered
to be well supported by the available information (US PHS 1964: US DHHS 1982).

Carcinogenesis in the respiratory tract is widely considered to be a multistep process
involving sequential changes in a cell from the normal to the malignant state. Extensive
experimental and human evidence is consistent with the multistage hypothesis. and
application of the new molecular and cellular biology techniques to the study of lung
cancer is providing further insights into the genetic mechanisms underlying the
development of this disease (Birrer and Minna 1988). Experiments with animals have
shown that agents may initiate or promote cancer. In animal experiments involving a
sequence of exposures to agents, those agents that cause cancer when administered
initially are referred to as initiators, whereas agents that promote the growth of initiated
cells are referred to as promoters.

Diverse multistep models of carcinogenesis have been developed (Farber 1983). The
age-incidence patterns for epithelial cancers such as lung cancer. which show that the
rates usually increase as a power of age. are also consistent with a multistage process

107


(Doll 1971: Doll and Peto 1978: Peto 1984; Day 1984). The bronchial epithelia of
sustained smokers show a progression of abnormality (Saccomanno et al. 1974). The
pseudostratified. ciliated epithelium becomes metaplastic and then dysplastic. Car-
cinoma in situ may develop and eventually become invasive (McDowell, Harris,Trump
1982). To the extent that cigarette smoking affects late as well as early stages in this
process, smoking cessation would be expected to have beneficial consequences on lung
cancer incidence. The epidemiologic evidence provides strong support for the an-
ticipated benefits of smoking cessation.

Cigarette smoking is associated with changes in the large and small airways, in the
respiratory epithelium and parenchyma. and in the numbers, type. and functional
capacities of inflammatory cells. The reversibility of these changes after smoking
cessation is germane to respiratory carcinogenesis and to the health consequences of
smoking cessation. This Section focuses on studies that have examined the effect of
smoking on the respiratory epithelium and on the cells in the lungs of current, former,
and never smokers. Additional relevant information is reviewed in Chapter 7 and in
previous reports of the Surgeon General (US DHHS 1984. 1986).

Smoking and Histopathology of the Airways

Extensive histopathologic evidence is available on the effects of smoking on the
airways of the lung. The association between smoking and premalignant changes in
the bronchial epithelium has been addressed by many investigators (US DHHS 1982).
Based on sequential examinations of exfoliative cytologic specimens from uranium
miners over a period of many years. Saccomanno and colleagues ( 1974) reported
evidence of squamous metaplasia progressing through increasing atypia to carcinoma
in situ and invasive bronchogenic carcinoma. Detailed observations have been made
on the histopathology of lung specimens obtained at autopsy (Auerbach et al. 1957.
1962a.b. 1963. 1964, 1972: Auerbach. Garfinkel. Hammond 1973).

In 1962. Auerbach and coworkers (1962a) reported that the frequency and intensity
of epithehal changes increased with the number of cigarettes smoked daily. In addition.
the$e investigators assessed changes following smoking cessation in postmortem
bronchial epithelial specimens from 72 ex-smokers and controls matched individually
with 2 controls per case (Auerbach et al. 1962b). One control was a current smoker
matched with an ex-smoker on age. occupation. residence. and smoking history. The
second control was a lifetime nonsmoker also matched with an ex-smoker on age.
occupation. and residence. Some type ofepithelial abnormality was found in 98 percent
of histologic sections from current smokers. 67 percent from ex-smokers. but only 26
percent from never smokers. Thi$ pattern persisted for many specific types of epithelial
abnormalities including absence of ciliated ceils. presence of atypical cells. and
presence of hyperplasia and goblet cells in glands (Table I ). The occurrence of
unciliated atypical cells. the most severe change before invasive carcinoma, was similar
among ex-smoker\ and never smokers but was considerably greater among current
smokers. The number of cells with atypical nuclei was reported to decrease with
increasing number of years since smoking cessation. When current smokers were
matched with former smoker5 of the same age at time of cessation. former smoker\

108


TABLE I.-Histologic changes (8) in bronchial epithelium by smoking status

showed fewer lesions. suggesting that the number of lesions decreased rather than
merely failed to increase after cessation of smoking.

Auerbach and colleagues (1964) also reported that among cigarette smokers. there
was a high degree of association between all types of histologic changes in the bronchi
and in the lung parenchyma. However, the lungs of ex-smokers were more similar to
those of never smokers than to those of current smokers with respect to cells with
atypical nuclei. In this study of 46 ex-smokers. 3 2 had few atypical cells in their
bronchial epithelium. Auerbach and associates (1964) suggested that with cessation of
smoking.cells with atypical nuclei gradually disappeared from the bronchial epithelium
and were replaced with normal cells.

Other Changes

Several reports have described levels of DNA adducts formed by the combination of
chemical carcinogens or their metabolites with DNA in the tissues of never, former,
and current smokers. Decline of DNA adduct levels in human lungs after smoking
cessation has been reported by Phillips and coworkers (1988). These investigators
utilized autoradiographs of chromatograms of "P-postlabeled digests of DNA from
lungs of current. former. and never smokers.  A linear relationship was observed
between number of cigarettes smoked per day and DNA adduct levels (Pearson
correlation coefficient. r=0.72, p<O.OOl). In addition. ex-smokers who had quit smok-
ing I to 3 months previously had adduct levels typical of the current smokers (12-14
adducts/lOx nucleotides), whereas those who had not smoked for 5 years or more had
adduct levels similar to those of never smokers (I .7-4.9 adducts/l OR nucleotides).
These investigators suggested that the reduced risk of lung cancer among ex-smokers
may be due to loss of the promutagenic lesions that initiate the process, in addition to
late-stage effects.

Randerath and colleagues (1989) also used a "P-postlabeling assay to study DNA
damage in relation to cigarette smoking. Adduct profiles and levels were determined
in nontumorous surgical specimens taken from patients with lung or laryngeal cancer.


Characteristic profiles were found in the laryngeal and lung tissues; levels of adducts
tended to increase with the amount of cumulative smoking. The study included only
three long-term former smokers with duration of abstinence ranging from IO to I4 years.
These subjects had low levels of adducts compared with current smokers.

Smoking Cessation and Lung Cancer Risk

Pattern of Changing Risk After Cessation

Numerous cohort and caseqontrol studies have documented a reduction in the
relative risk of lung cancer among former smokers compared with current smokers,
The findings of selected studies are presented in Table 2. Former smokers in these
studies experienced a IO- to 800-percent increase in risk of lung cancer compared with
never smokers; however. compared with current smokers, former smokers showed a
20- to 90-percent reduction in risk.

The relative risk estimates provided in Table 2 group former smokers with varying
durations of abstinence from smoking. However, the number of years since cessation
has a strong effect on risk of lung cancer among former smokers: in studies assessing
risk by duration of abstinence. the reduced risk has been evident within 5 years of
cessation compared with continued smoking. and the benefit of cessation has increased
as the duration of abstinence lengthened. However, in most of the studies, the risk of
lung cancer among former smokers remained elevated above the risk among never
smokers. even in the longest periods of abstinence evaluated. In many studies. risks
among former smokers were higher than among continuing smokers during the first
few years after stopping smoking. This pattern of risk reflects cessation by individuals
who quit smoking because of symptoms and illness before the clinical diagnosis of lung
cancer (Chapter 2; Haenszel. Loveland. Sirken 1962; Doll and Hill 1964; Kahn 1966).

Table 3 summarizes standardized mortality ratios of lung cancer among former
smokers by years of abstinence. as reported in five cohort studies: British physicians.
U.S. veterans. Japanese males, and the American Cancer Society Cancer Prevention
Studies. ACS CPS-I and ACS CPS-II. These studies varied in the length of followup.
the extent of information obtained on smoking history. and the number of lung cancer
cases. Compared M ith never smokers. former smokers who had been abstinent for JO
to 20 years or more showed a varying extent of risk. reduction among the studies. In
the British Physicians Study. U.S. Veterans Study. and ACS CPS-II, former smokers
who had been abstinent for IS yearj or more showed an 80- to 90-percent reduction in
risk compared with current smokers. The percentage reduction in risk was slightly
lower among the Japanese cohort and higher in AC'S CPS-I.

Results from selected ca\e-control studies are shoun in Table 3. As in the cohort
studies, former smohers who had been abstinent the longest experienced increased rish
compared with nevter smokers. but substantially reduced risk in most i;tudies compared
with current smokers.

Thus, reduction in risk of lung cancer after smoking cessation has been observed in
numerous cohort and caseecontrol studies conducted in the United Kingdom (Doll and
Peto 1976: Alder\on. Lee. Wang 1985). the United States (Kahn 1966: Hammond 1966:


TABLE 2.-Relative risks of lung cancer among never, former, and current smokers in selected epidemiologic studies

Hammond ( IYhh)

Kahn t 1966)

Canadian Department of
National Health and Welfxe
( IYhh)

Population







ACS CPS-I

US veteran4

Canadi;m malea

Suhg'oup

Never \mohcr\







    I .o

    I .o

    I .o

Former smoker\



I-IY     20
clp/day   c igiclay
- -
2.0      7.`)

     3.7

     h. I

Cederlof et 31. t 1975)

Doll and Pet0 ( I Y7h)

Doll et ill. t IYXO)

Wigle. Mao. G-xc
(IYXO)

wu Cl al. t IYXS)

Carstewa Perd~npen.
Ehlund t IYX7)

ACS
tunpubli\hed
tabulation\)

                Melrs                  I .o                0. I                7.X
                Ft3dt3                 I .o                I .5                45

British mule phywians                         I .o                4.3               I0.J

Brtti\h female phyclclan\                        I .o                3.?               6.4,'

Alkrtic (Canada) cancer   Male\                  I .o                6.5                IO.4
patlent\             Female\                 I.0                7.1                5.2

Lo\ An@\ (CA) white\  Squamou\                I .(I                7.7               35.3
                 Adcnoc:lrcillonta            I .o                1.2                1. I

Swrdl\h males                              I .o                I.1            1.5"


ACS CPS-II           Male\                  I .(I                X.Y               21.3
                Female5                 I .o                4.x               17.1


TABLE 3.-Lung cancer mortality ratios among never, current, and former smokers by number of years since stopped smoking
     (relative to never smokers), prospective studies

                                    Smokmg ttatu\

Referwce              Populatwn

and yr \ince
uopped rmokmg

Mortality ratios (N)"

Doll and Pcto t I Y7h)

Roget and Murray t I YXO)

Never smoker\
Current moher\
Former smoker\
       l-4
       S-Y
      IO-14
        >I5

Current smoker\
Former woher\
       IL.4
       S-Y
      lOLl4
      15-l')
        x!o

Current waker\
Former smoker\
       l-4
       S-Y
        >I0

I .o (7)
15.X(123)


lh.O(l5)
S.Y(l')
5.3 (Y)
7.0 (7)

11.3(2.6OY)


1x.x (47)
7.7 (X6)
4.7 (I(H))
4.x (I IS)
2.1 (123)

3.x


4.7
2.5
I .4

IY.Sl-71,Dyr followup:
data on former smoker\ In
wmmary form

195449, 16-yr followup


TABLE 3.-Continued

Reference              Population

Smoking status
and yr since
stopped wloking

Hammond ( 1966)

ACS CPS-I male%

Never wwkerh
Current v~x~k.er~
f%mer \moher\
        <I
       ILit
      S-Y
        >I0

ACS (unpuhll\hcd
tuhulatlww)

ACS CPS-II malrb

Never w~ohers
Current smokers
Former smoker\
        <I
       I-?
       3-s
       &IO
      I l-15
        >Ih

Mortality ratio5 (N)"

Comments

I-l')
up/day

IYSY-67. 7.5.yr followup.
men aped SO-69

I .o (32)       1.0(37)
6.5 (X.01      13.7(351)

7.7 (`I)       2Y.I (73)
4.6 (5)       12.0(3X
I .o ( I )       7.2 (22)
0.4 ( I ,       I.1 ts,

I-20           221
cig/dny       clg/d;ly

I.0 (XI)       I .o (XI,
1x.x (60X)      X.9(551)

26.7 (32)      50.7 (63)
??.4 (7 I )      31.2(117)
16.5 (X2)      20.`) (Yh)
x.7 (X01      IS.0 ( IOh)
h.0 (6Y 1      I?.6 (Y5)
3.1 t I441      5.5 (I 121


TABLE .X-Continued

Never \mohcr\
<`urrcnt wiokw
I%rmcr \mohcr\
        <I
       l-2
       3-s
       610
      I l-l.5
        Zlh

l-1')          >20
+/day      Cl@i)

I .o ( IX l )
7.2 ( 145)

7.Y (3
9.1 (13,
2.0 (7)
I .o (4)
I.5 (6)
I .4 (23)

I .o ( IX I )
16.3 (334)

34.3 (3 I I
IY.5 (42)
14.6 (42)
Y.I (32)
5.Y (20,
2.6 (IX)


TABLE 4.-Relative risks of lung cancer among former smokers, by number of years since stopped smoking, and current
      smokers, from selected case-control studies

Reference

Popuhtion

Definition of
former smoher

Smoking status
and yr \ince
wpprd



Graham and Levin
(1971)

New York          At hospital admission

Never smoker\
Current vnokers
Former smoker5
       0-03
     >().%I
      >I-.?
      >3-IO
       >I0

Wigle, Mao, Grace
(1980)

Correa et al. (1984)

Alberta. Canada, cancer
patient5

At mtervww

NR

NWCI- \mohcln
Current \moher\
Former amohers
      3-s
       6X
       >20

Rewlts

Aci.juatment"

Male\

Crude

I .o
X.X

     42 2
     z 3 3
     IO.0
     3.3
      I.3

Mole\     l+males

  0. I       0.1
  I 0       I .o

3.4       0.9
0.7       0.s
0.7       0.5
0 2       0.4

M;lle\ d f?nlule\

     I .o
    I2 h

77
7.0
3.9


TABLE 4.--Continued

Deflnltlon of
former maker

Smoking status
and yr since
stopped

Results

Adjustment'l

AItl~r\~~n. Lee. W;rnp
(19X.5)

(;;I0 c, al , I')XX)

NK

Never makers
Current \mokrr\
Former smoker\
       I-2
      5-10
       >I0

Never smoker\
Current \mokrr\
Former smokers
       IL4
       s-9
       2 IO



Never smohw
Former smokers
       <IO
      1%19
      ?(k-?9
       230



Current smokers
Former smoker\
       I4
       >5

Mules
0. I
I .o


I .x
0.4
0.3

Female\
0.2
I .o


2. I
0.7
0.3

Males     Female\
) .o       I .o
3.9       2.9


6.9       7.2
3.1       3.9
LI       3.2

   Male\
     I .o


    I I .9
     6.1
     3.7
     I .9

Males     Femall3

I .o       I .o


I.?       2.0
0.6       0.9

Age

Age and
educatwn

At lrab~ I yr at time
of lntervleu

NK

Duration of
\mokmg


TABLE 4.--Continued

Reference             Population

     Defimtion of
    former \moher
~-.__~

    Smoking %13tu\
     and yr Gnce
      stopped
-~~~ __. ~~

Lubin et al. (1984a)

Pathak et al. (1986)

European casexontrol
study

New Mexico

At interview

Current smoker\
Former hmokerk
       1-4
      s-9
      l&l4
      IS-19
     2%?4
       x.5

AI least I yr before
interview

Current smoker\
Former smoker\
       S
      IO
      20



Current smokers
Former smokers
       I-S
       6-10
       >I0

Damber and Larson
(19X6)

Swedenh

NR

Males
I .u

I.1
0.7
0.6
0.4
0.4
0.3

Female\
I .o


0.9
0.7
0.4
0.5
0.5
0.3

Duration of
smoking

  Male\
S6.5      >hS
I .o       I .o


0.5       0.7
0.2       0.5
0. I       0.3

  Male\
    9.S


    73
    3.0
    2.0

Number of
q/day

Age


Graham and Levin I97 I; Pathak et al. 1986). Canada (Wigle. Mao. Grace 1980). Europe
(Lubinetal. 1984a;DamberandLarsson 1986).Asia(USDHHS 1982:Gaoetal. 1988).
and Latin America (Joly. Lubin. Caraballoso 1983). Although only a few studies had
information on female former smokers, the pattern of risk reduction was similar to that
observed for males. Decrease in risk after smoking cessation also has been reported
for each of the major histologic types of lung cancer (Wynder and Stellman 1977; Lubin
and Blot 1984: Benhamou et al. 1985: Higgins and Wynder 1988) (Table 5 and Figure
I ). Higgins and Wynder ( 1988) found that the decline in risk after cessation was more
consistent for Kreyberg I tumors (primarily squamous cell, small cell. and large cell
cancers) than for Kreyberg II tumors (primarily adenocarcinomas and bronchiolo-
alveolar carcinomas) (Figure I ). Smokers of filter and nonfilter cigarettes (Wynder and
Stellman 1979: Lubin et al. 1984b) and of other tobacco products (Joly. Lubin.
Caraballoso 1983: Lubin et al. 1984b; Damber and Larsson 1986; Higgins, Mahan,
Wynder 1988) have reduced lung cancer risk following cessation (Table 6). Although
the findings of the reviewed studies uniformly indicate lower risk among former
smokers. the magnitude and rapidity of the risk reduction with smoking cessation varies
among the studies. This variation has several potential explanations.
First, years of abstinence among those who stopped smoking for the longest time
interval varied from 5 to 25 years or more. Second, although former smokers have a
risk of lung cancer between those of continuing smokers and never smokers. the pattern
of declining risk as duration of abstinence lengthens has not been fully characterized.
The small number of former smokers in some studies limits the precision with which
the decline in risk can be described, particularly for the longer durations of abstinence.
Third. aspects of the active smoking history. including cumulative smoking exposure
up to the time of quitting. age at initiation. years of smoking. number of cigarettes
smoked per day. inhalation practices. types of cigarettes and other tobacco products
smoked, age at smoking cessation. and the reason for stopping, may modify the risk of
lung cancer after cessation (Chapter 4. see section on Effect of Antecedent Smoking
History). The varying extent to which these factors havJe been considered in analyzing
the effect of cessation may partially explain the differences in risk observed in former
smokers among the studies. As discussed below. failure to adjust for previous smoking
history may exaggerate the benefit of smoking cessation. but adjustment for cumulative
smoking history also may result in overadjustment of the risk estimate (Chapter 2).
Fourth, the studies vary in the definition of former or es-smohers and in the analytic
treatment of former smohers u ho have recently stopped smoking. In the case<ontrol
studies. former smohers have been defined as individuals who were abstinent at the
time of interview. at the time of cancer diagnosis. or at some other reference point (e.g..
I year before diagnosis of lung cancer and a comparable time for controls).
To reduce the bias introduced by quitting because of illness. fomler smokers who
stopped smoking after developing symptoms ordisease may be excluded from analysis.
Information on the reason for cessation was collected only in some studies. and persons
with symptoms at cessation have not been handled unifomlly in the published literature.
Finally. results of the relevjant studies are not totally comparable because the risks of
former smokers were compared u ith those of never smokers in some studies and with
continuing smokers in others.


TABIX S.-Relative risks of lung cancer among never, current, and former smokers, by number of years since stopping smoking

   Malt!\
Krq hcrf I> ,I?
I        II
I .o       I .o
31.3      IO 7

  Ft!lll;llt2\
Kreyherg type
I       II
I .o      I .o
10.5      4.4

52.X      I-t.?             13.6      6.7
74.0       5.0             6.2      3.6
17.1       6.6             5.1      4.1
13.7       5.-J             x.x      5.6
5.0       I.7                     O.`J
   Mnh
Krc?tm$ t>t>c
I        II
I 0       I .o


.I-&.(>       6.1
I'.'       2.1
IO 9
0.J       I .o
4.2

M;Itc\                 I;CllldC\
ADEN           sy    ADENO
    I .o              I .o      I 0

t 0
0.x
0.6
0.0
0.5

I.1      0.7
0.0      I .o
0 4      0.4
0.4      I .7
0.3      0.3


TABLE &-Relative risks of lung cancer among never, former, and current smokers by types of tobacco products smoked

Never smoker\

Former smokers

Current smoker\

C`Igarettc~ only                 I .o              6.Y             16.0
CIg;ir\ only                   I .o              2.5             3.1
Pipes only                   I .o              0.7              I .9
Clfars and pipe\                t .(I             2.4             x.5
Mixed woher\                I .o              S.1             10,s

Y r Gnce stopped
I4       2.5

0.6       0.7
4.4       0.0
2.0       0.Y
t .2       0.8

I .o
t .o
I .o
I .o

C`lgarelte\ only"
Plp13 only

Y r since \topped
t-10      >I0

S.0       1.2
5.0       4.5

9.5
x.0


KREYBERG I (N-330)

MEN

30


25


20

15


10


5


0

E

L

i4 t KREYBERG II (N=204)
Y 15
d             n    r-l r

35


30


25


20


15


10


5


0


15


10

9  10
F:
25
20

5

0

1  -   11  -  21  -  31  -  241
NUMBER OF CIGDAY

Yr of abstinence

WOMEN

KREYBERG I (N-951

KREYBERG II (N=lOO)

01-4 05-9 810-19 sl20-29 * >30

FIGURE l.-Risk of lung cancer by number of cigarettes smoked per day
     before quitting, number of years of abstinence, sex, and histologic
       types

SOC'RCE: Hlggn\ and W>ndrr (198X)


Although this review has emphasized the results of cohort and casexontrol studies.
descriptive data on lung cancer mortality in the United States are consistent with a
beneficial effect of the declining prevalence of cigarette smoking. Devesa. Blot, and
Fraumeni ( IYW) described declining mortality rates for lung cancer at ages belov, 15
years. The decreases were greatest among white men but also occurred among white
women and blacks of both sexes.

Effect of Antecedent Smoking History

The preceding Section reviewed epidemiologic studies describing the pattern of lung
cancer rish following smoking cessation.  This Section considers factors related to
smoking that plausibly could modify the effect of cessation on lung cancer risk: these
factors include the duration of smoking. daily cigarette consumption. inhalation prac-
tices, types of tobacco products smoked. and age at cessation.

Duration of Smohing

Duration of smoking prior to cessation is a potentially important modifier of the
pattern of risk reduction in ex-smokers. Graham and Levin (1971) examined the rish
of lung cancer associated with increasing durations of abstinence and with stratification
by duration of smoking (130 or 23 I years and 5-I-10 or 231 years). The decline in risk
associated with stopping v~as greater for those who had smoked for shorter periods than
for those who had smoked for longer periods. Similar results were reported by Lubin
and colleagues ( 19x41). who determined the rish of developing lung cancer by time
since stopping hmohing (0. I--1. 5-Y. and 210 years) and total duration of smoking
( I-19. 20-N. 404Y. and 23) Jears). In each category of smoking duration. the rish
of developing lung cancer decreased as the number of j'ears since stopping smohing
increased. but the rate of decline LI as greater among those who had smohed for a shorter
time. Among men who had smoked for I to IY years. the rish ofdeveloping lung cancer
after IO ycurs of abstinence dropped to Ie\s than one-third of that among current
smohers. On the other hand. t'or men 1% ho had smohed 50 ! ears or more and stopped
for at least 10 \`ears. the rish M as still YO percent otthat t`or men LI ho continued to smohe.
This analysis. which matched for age and controlled for both duration of smoking and
length of abstinence. introduces too man! \anahlcs i'or the temporal dimensions 01`
cifarette use (Chapter 7). B! simultaneously considering attained age. duration ot'
smohing. and length of abstinence. the anal> tic model incorrect11 forces former
smohers to ha\,e ;I ! oungcr age of starting to smohe than current smohers.  Ill ;I
case--Control stud!, in Sweden. Dambcr and Lars\on ( I YX6) also found higher rt'lati\.e
risks among t'onncr smohcrs of pipes and cl,,
                   `o,lrettes u ho had smohrd longer.
Brown and Chu ( lYX7) ~ggestcd that t'ailure to ad.iu\t for pre\ ious duration ot

smohing ma\ result in rish e\timatc\ i'or former smohers that are too ION and thus
exaggerate the henei'ith of smohing cessation. Based on reanalysis of data from the
large European case<ontrol stud!. Brou II and Chu ( I 1~x7) reported that the correlation
between duration ofsmoking and time since stopping smohing fore\-smoker\ M a-0.6.
indicating that men u ho had stopped \mohin, (1 t`or man\ \ ears had also \mohcd t'or le>s
                                       _ .


\
\
\
\
%
  `4 4

`\\
           \
            \
             \
      `A---- --&\
WITHOUT ADJUSTMENT FOR  ' \ \
  SMOKING DURATION           \ \ \

-  "' I
     0   k   lb   1;   $0   2k   io :
   YR SINCE QUIT SMOKING

FIGURE 2.-Relative risk of lung cancer among ex-smokers compared with
     continuing smokers as a function of time since stopped smoking,
      estimated from logistic regression model, pattern adjusted for
     smoking duration compared with pattern unadjusted for duration
SOCiRCE. Hroun and Chu (101171

time than men who had stopped for a shorter time. The relative risk of lung cancer
continued to decrease sharply with increasing years of abstinence without adjusting for
smoking duration. whereas the decreasing relative risk plateaued when adjusted for
duration of smoking (Figure 2). The difference in this pattern was most noticeable for
increasing years of smoking abstinence. For those who had stopped smoking for 27
years or more, the relative risk compared with continuing smokers was 0.30 when
adjusted for duration, but 0.17 when no adjustment was made. However. control for
previous duration of smoking (or cumulative previous smoking history) in determining
the risk of lung cancer among former smokers may constitute overadjustment if age
and duration of cessation also are included in the model (Chapter 2).

In summary, only limited analyses address the effect of duration of previous smoking
on the decline in risk following cessation. The data point to less decline of relative risk
following cessation, comparing longer term with shorter term studiej. but additional
investigation is needed.

123


Daily Cigarette Consumption

Previous smohing intensity or number of cigarettes smoked per day also affects the
pattern of risk reduction after smoking cessation. In the U.S. Veterans Study. the
mortality ratios for lung cancer were 1.3 I, 3.37, 8.31. and IO.05 for ex-smokers who
smoked I to 9. IO to 20.2 I to 39. and 40 cigarettes or more per day, respectively (Kahn
1966). The pattern of lung cancer rish reduction by years of smoking abstinence and
number of cigarettes smoked has been reported for several studies. In ACS CPS-I and
ACS CPS-II (Hammond 1966: Garfinkel and Stellman 1988). the decline in risk with
stopping smoking showed a comparable proportional reduction in risk among those
who had smoked less (Table 3). In the European case<ontrol study (Lubin et al.
1984a). men who had stopped smoking for IO years or more, but had previously smoked
30 cigarettes or more per day. had a M-percent risk of developing lung cancer
compared with corresponding current smokers. whereas men who had smoked 1 to 9
cigarettes per day had a 67-percent risk compared with corresponding current smokers.
Similar result\ were observed for female ex-smokers (Lubin et al. 1984a). As pre-
viously discussed. duration of smoking was considered in these analyses. Thus, heavier
smokers have less reduction of lung cancer risk following cessation than smokers of
fewer cigarettes per day.

Inhalation Pmctices

The pattern of lung cancer risk hy year\ of \mohing abstinence and by inhalation
practices (i.e.. frequenq and depth of inhalation) has examined by Lubin and col-
leagues ( 1983a). Their analysis indicated :I somewhat greater reduction in risk for those
ex-smokers who had inhaled le\s often or less deeply. Among men who had stopped
smoking for IO year, or more. relative risk by reported frequency of inhalation
compared with current smokers was lowest for those uho had rarely or never inhaled
(relative risk (RR)=0.30) and for those whose depth of inhalation was reported a\ onl!
slight or not at all (RR=O.37). In comparison. the relative risk after 10 bears or more
of abstinence was highest for those who had inhaled all the time (RR=O.50) and for
those uho had inhaled deeply tRR=O.47). The same pattern ~\as ob\er\,ed among
women.

Different Tobacco Products

Differences in the reduction in ri\k folIoMing cessation also have been investigated
by types of cigarette\ smohed. A loner ri\h of lung cancer has been obser\,ed fol-
mohers of filter cigarettes compared with smohcrs of nonfilter cigarettes (US DHHS
lYX7. IYXY: Wynder and Kubat IYXX). a pattern suggesting that the reduction in ri4h
among former smoher\ ma\' be more apparent for filter cigarette \mokerh,. Ho&ever.
no significant difference> in the trend of ri\h reduction by years of hmohing abstinence
(0. 14. 5-Y. and 210) and b>, type of cigarettes moked (filter. mixed. nonfilter) \\erc
observed by Lubin and coworher\ ( 19XlhJ in the European case-i'ontrol stud>. Among


men. the relative risk for former smokers after stopping smoking for IO lears or more
has 0.4 for filter cigarette smokers. 0.3 for nonfiitercigarette smoher5. and 0.5 for mixed
filter and nonfilter cigarette smokers.  These data were collected in five western
European countries from 1976 to IYXO: the tar yields of the products smohed were
relatively high in comparison with cigarettes currently smoked in the Ilnited States
(Lubin et al. IYX3b).

In most studies, cigar and pipe smokers have louver lung cancer risks compared with
cigarette smokers (US DHHS IYX2). Former smohers of only pipes or cigars also
showed an intermediate risk of lung cancer compared v. ith current smokers and never
smohers of these tobacco products (Table 6). In the U.S. Veterans Stud). the lung
cancer mortality ratio. compared with never smohers. was I .67 among current smokers
who used only pipes or cigars and 1 .SO among former smoker\ (Kahn lY66). In a
case-control study ofsmoking-related cancers conducted in the United States. Higgins.
Mahan. and Wynder (1988) reported that ex-smokers of cigars only showed a relative
risk of 1.5 compared with 3.1 among current smokers of cigars only. The relative rish
was 0.7 among ex-smoker\ of pipes only compared with I.Y among current pipe
smokers only. Analysis of the pattern of risk among ex-smokers of cigars and pipes
only by considering the amount and duration smoked prior to smohing cessation
revealed similar patterns of risk reduction among light and heavy smokers.

Lubin. Richter. and Blot ( 1984) also examined the pattern of risk reduction by years
of smoking abstinence (0. I--1, 25 years) and types of tobacco smoked (cigars onI!,.
mixed cigar and cigarette smokers, pipes only. and mixed pipe and cigarette smokers).
No apparent differences were observed in the estimated rishs. ivhen analyred by
tobacco products. among those who had stopped smoking for at least 5 years. but the
numbers of cases who smoked cigars only and pipes only were quite small. On the
otherhand. Damber and Larsson ( 1986) reported that the decrease in relative risk among
ex-smokers was less pronounced in smokers of pipes compared with cigarette smoker\
only in a case-control study conducted in Sweden. However. in this population. the
risk of lung cancer for pipe smokers (RR=6.9) was similar to that of cigarette smokers
(RR=7.0).

In summary, these analyses. limited by the sample sizes within strata of types of
products smoked, do not characterize precisely the changing lung cancer risk following
cessation for smokers of various tobacco products.

Effect of Age at Cessation

Several researchers have suggested that the reduction in rish after smoking cessation
may differ by age at cessation. Wynder and Stellman ( 1979) reported that the reduction
in risk after cessation was appreciably greater for people aged 50 to 6Y than for those
70 or older. However. only data for those aged SO to 69 were presented in this
publication. Pathak and associates (1986) also reported a strong interaction between
age and duration of cigarette smohing. Risk of lung cancer among ex-smokers was
compared with that of current smokers with adjustment for the amount smohed. For
ex-smokers less than 65 years of age. the estimated relative risks compared u ith current
smokers declined to 0.39. 0.14, and 0.06 for 5. IO. and 20 years of smoking abstinence.