mouth and pharynx” (48). Since most. people who drink large
amounts of alchohol regularly are also heavy users of tobacco, it is
difficult: to identify the relative contribution of these two factors or
the role of the nutritional problems often associated with heavy
alcohol use.

Additional data have been reported by Moore (62), on patients
developing second primary mouth and throat cancers, after having
been cured for at least three years prior to development of the cancer.
These patients were all asymptomatic for at least three years prior to
development of the second cancer. Of 117 patients with adequate
smoking histories only 4 of 43 (9 percent) who quit smoking after
the first cancer, developed a new primary. On the other hand, 27 of 74
patients (36 percent) who continued to smoke developed a second
primary cancer. These data support the important contribution of
smoking to the etiology of mouth and throat cancer,

Roth, et al. (73. 74) recently have shown that the dye-binding
capacity of DNA of oral epithelial cells is significantly enhanced in
cigarette smokers in contrast to nonsmokers, probably reflecting an
increase in the DNA content of oral epithelial cells in smokers. This
Suggests some alteration in the DNA which may be a factor in oral
carcinogenesis. Smokers had values of dye-binding capacity inter-
mediate between nonsmokers and 21 patients with proven oral cancer.
Those smokers who refrained from smoking for up to nine months
showed a significant: decrease towards more normal values,

Tt is clear that people who use tobacco have higher rates of oral
cancer than those who do not. Research is needed to identify the dose
relationships, to determine whether or not there are dosage thresholds,
and to clarify the relationships between dosage, style of tobacco use,
and part of the mouth affected,

It seems likely that factors such as alcohol consumption, nutritional
problems, and oral hygiene may be interrelated with the tobacco habit
in a fairly complex pattern. More research is needed to clarify these
relationships.

For patients with oral cancer, and probably for those at a high risk
of oral cancer because of other exposures, cessation of tobacco use can
make an important contribution to reducing the risk of a new primary
cancer,

CANCER OF THE LARYNX

Cancer of the larynx is mainly a disease of male smokers, Of the
2,629 deaths in 1965, over 88 percent were men. The 1967 report noted
that the death rate for cancer of the larynx had not increased signifi-
cantly since 1950. The incidence rates, however, have shown a steady
increase since 1935.

101
LARYNX

 

Incidence rates per 100,000 population

a on

» om,
~ oon ” em ot
esa Ng ett et Te" Pd “weeny, -

0 I i l

1935 1940 1945, 1950 1955 1960
Years

 

 

 

=== =6Male -—- Female

Ficture 3—Age-adjusted rates of the incidence of cancer of the larynx, for males
and females: Connecticut, 1985-1962
Source : Eisenberg et al. (24).

The American Cancer Society (2) estimates the occurence of 6,000
new cases of cancer of the larynx in 1968 but only about 2,800 deaths,
due to relative curability of this disease if diagnosed early.

Several retrospective studies have again shown the extremely high
rate of smokers [98 percent (86), 92 percent (75) ] among patients with
cancer of the larynx.

CANCER OF THE ESOPHAGUS

As reported in the 1967 Report (92) the death rates for cancer of
the esophagus have increased only slightly in the period 1950-1964.
The large scale prospective studies (18, 19, 34, 46) showed mortality
ratios up to 11 in heavy cigarette smokers, while pipe and/or cigar
smokers had ratios up to 5.

Preliminary data from a prospective study (37) in Japan also indi-
cate an increased frequency of death from cancer of the esophagus
among smokers as compared to nonsmokers.

No further information has become available on the relationship of
esophageal cancer to aleohol and/or other confounding variables as
discussed in the 1967 report.

102
CANCER OF THE PANCREAS

The 1967 report implied a relationship between smoking and pan-
creatic cancer due to the somewhat higher mortality ratios observed in
three of the large scale prospective epidemiologic studies.

The American Cancer Society estimates that deaths due to cancer
of the pancreas will total 18,000 in 1968 with a male/female ratio of
approximately 3:2. The overall death rate for cancer of the pancreas
has shown a steady rise; from 7.2 to 8.4 in males (+17 percent) and
44 to 4.9 (+11 percent) in females, for the time period 1953-55 to
1963-65 (2). The incidence rates have increased almost 50 percent in
males since 1935, with no apparent increase for females.

In the past year, preliminary evidence from two retrospective studies
(43, 102) has shown that only 10 percent of the patients with cancer of
the pancreas are nonsmokers. The risk of developing cancer of the pan-
creas appears to increase in proportion to the amount smoked.

Preliminary data from a prospective study (37) in Japan also shows
a significantly higher frequency of deaths from pancreatic cancer
among smokers as compared to nonsmokers.

PANCREAS

 

 

Incidence rates per 100,000 population

 

0 ! ! ! !
1935 1940 1945 1950 1955 1960

Years

 

 

— Male eem= Female

Fieure 4—Age-adjusted rates of the incidence of cancer of the pancreas, for males
and females: Connecticut, 1935-1962.

Source: Hisenberg, et al. (24).

315-181 O—68——S 103
These studies strengthen the earlier indications of an association be-
tween smoking and pancreatic cancer, but further research is needed in
this area to elucidate the significance of this association.

GENITO-URINARY CANCER
CANCER OF THE BLADDER

As stated in the 1967 Report, there has been no increase in male or
female death rates for cancer of the bladder over the 15 year period
1950-1964. However, the incidence rates for males have increased over
75 percent in the 25-year period from 1935-37 to 1960-62, and about
26 percent in the 15 year period from 1945-47 to 1960-62.

Deeley, et al. (16) reported on a retrospective study of 127 patients
with cancer of the bladder and 126 patients with lung cancer, all
matched with controls. The smoking “factors” (amount times duration
of smoking) were significantly greater among cases than controls for
both cancer sites. Even by age-groups, the “mean smoking factor” for
either cancer was higher for cases than for controls. Preliminary data

 

 

 

 

BLADDER
25
20-—
ce
2
a
3
a
°
a
oS 15 F-
8
8
&
a
“
&
a
© 10
g
c
a
3
e
o*. a
* ow 7X oo * / ‘ -4
~ af 7 *, o eo x ae
5 ap Na Nea aiid aed rd ww wot
‘wa!
Q | | J | |
1935 1940 1945 1950 1955 1960
Years
owe Male eee am Female

FIcURE 3—Age-adjusted rates of the incidence of cancer of the bladder, for males
and females: Connecticut, 1985-1962.

Source: Eisenberg, et al. (24)

104
from a prospective study (37) in Japan shows a higher frequency of
deaths from bladder cancer among smokers.

Certain amino acids, as found in tobacco, form trace amounts of
alpha- and beta-naphthylamines upon pyrolysis (59). The latter agent
is an established bladder carcinogen. So far, however, only its isomeric
alpha-naphthylamines has been identified in cigarette smoke (60, 67).

Further investigation is needed on the carcinogenic metabolites of
tryptophan which have been shown to be increased in the urine of
cigarette smokers (92).

CANCER OF THE KIDNEY

The 1967 Report did not mention the association between smoking
and cancer of the kidney.

The U.S. Veterans study (46) shows increasing mortality ratios for
cancer of the kidney with the amount of cigarette smoking. There is
no apparent relationship with pipe and/or cigar smoking.

TABLE 3.—Mortality ratios and death rates Jor cancer of the kidney in
U.S. veterans, by age, type and amount smoked for current smokers
only

 

Pipe

and/or | Cigars
10-20 21-39 40 and cigars

over

 

Pipe

 

 

 

Mortality ratios_____ 1. 00 .97 | 1.634) 168 | 2757 115 77 1, 32

Death rates:

 

 

 

Age 45-54... 222) 2 2 fej) Jee |e
Age 55-64.______ 8 5 8 10 26 5 7 2
Age 65-74.______ 14 7 15 27 13 14 | 2 25
Age 75~84.______ 7 [------|- eee fe 40 |

 

Source: Kahn, H. A. (46).

TABLE 4.—Mortality ratios and death rates for cancer of the kidney in
male cigarette smokers, by specified age groups

 

 

 

 

 

Cigarette smokers
Age 45-64 Age 65-79
Mortality ratios._____..2---- 88. 1. 42 | 1. 57
Death rates_._.--2 22 1 (4)6 | 1 (15)23

! Numbers in parentheses indicate death rates for persons who have never smoked regularly.
Source: Hammond, E. C. ($4).

105
Hammond (34) has also demonstrated higher mortality ratios in
cigarette smokers for cancer of the kidney.

Preliminary evidence from a retrospective study in progress (102)
suggests that cigarette smokers, especially those who smoke over 35
cigarettes a day, are over-represented in those patients with cancer of
the kidney. More research should be done to try to ascertain if there is
a meaningful relationship between smoking and cancer of the kidney.

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106

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