mout,h 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
t'he role of Ihe nutritional problems often associated with heavy
alcohol use.

,4dditional data have, been reported by Moore (&?), on patients
developing second primnrv mouth and throat cancers, after having
heen cured for at. least thrie 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 Ji-1 (0 ljercent) who quit smoking after
the first, cancer, developed a new ljritnary. On the other hand, 27 of 74
patients (36 percent) who continued to smoke del-eloped a second
primary cancer. These data supl)ort the important contribution of
smoking to the etiology of mouth and throat cancer.

Roth, et al. (73. 74) recently have shown that the dTe-binding
capacit,y of DSA of oral epithelial cells is significantly enhanced in
cigarette smokers in contrast to nonsmokers, probably reflecting an
increase in the DSA content of oral epithelial cells in smokers. This
suggests some alteration in the Ds.1 which ma\- be a factor in oral
carcinogenesis. Smokers had \-alues 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 I-alues.

It is clear that people who use tobacco hare 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 mas be interrelated with the tobacco habit
in a fairly complex pattern. More resenrrh 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.

CA?;CER OF THE LARYNX

Cancer of the larynx is mainly a disease of male smokers. Of t,he
2,629 deaths in 1965, over 88 percent, were men. The 1067 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 19%

101


FIWRE &.Ige-adjusted rates of the incidence of cancer of the larynx, for males
           and females : Connecticut, 193&1962
SOURCE : Eisenberg et al. (24).

The American Pancer Society (2) estimates the occ.urence of 6,000
new cases of cancer of t.he larynx in 1968 but only about, 2,800 deaths,
due to relative curability of t,his disease if diagnosed early.
Several retrospective studies have again shown the extremely high
rate of smokers [ 98 percent (86)) 92 percent (75) ] among paCents with
cancer of the larynx.

CAKCER 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, 4s) showed mortality
ra.tios 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 alcohol and/or other confounding variables as
discussed in the 1967 report.

102


CANCER OF THE PANCREAS

The 196'i report implied a rellat,ionship between smoking and pan-
creatic cance,r due to the somewhat higher mortalit,y ratios observed in
three of the. large scale prospective epidemiologic studies.
The ,Imerican Cancer Society estimates that. deaths due to cancer
of the pancreas will total 15,000 in 1968 with a male/fe.male ratio of
approvimate.ly :< : 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
et.4 to 4.9 ( fll percent) in females, for the time period 1953~55 to
196-65 (a). The incidence rates have increased almost 50 percent in
males since 1935, with no apparent increase for fernala.
In the past. year? preliminary evidence from two retrtrqwtive studies
(&3,102?) has showi 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 proport ion to the amount smoked.
Preliminary data from a prospective study (37) in Japan also shops
a significantly higher frequency of deaths from pancreatic cancer
among smokers a.s compared to nonsmokers.

PANCREAS

      - Male    --- Female

FIGURE -l--Age-adjusted rates of the incidence of cancer of the pancreas, for males
        and females : Connecticut, 19X*1962.
SOURCE: JGisenberg, et al. (24).

?J5-Ii31 0-68-S                            103


These st.ndies st,rengthen the earlier indications of an ass&&on be-
t\wen smoking and pancreatic cancer, but. further research is needed in
this are.a 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, t.he incidence rates for males have increased orer
75 pe.rcent in the 25-year period from 1935-37 to 1960-62, and about
26 percent. in the 15 year period from 19454i to 1960-62.

Deeleg, et al. (16) reported on a retrospective study of 127 patients
with cancer of the bladder and 126 patients wi-it.h lung cancer, all
matc.hed 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 n-as higher for cases than for controls. Preliminary data

FICLTLE Z-Age-adjusted rates of the incidence of cancer of the bladder, for males
             and frmalw : (`onwcticut, l%~l!W2.

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 be&naphthylamines upon pyrolysis (59). The latt.er agent
is an estab1ishe.d bladder carcinogen. So far, howewr, only it.s isomeric
alpha-naphthylamines `has been identified in cigarette smoke (GO. 67).
Further investigat,ion is ne.eded on the carcinogenic metabolites of
tryptophan which have been shown to be inere.ased in the urine of
cigarette smokers (9%`).

CANCER OF THE KIDNEY

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

The U.S. Veterans study (4~) shops 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 for cancer of the kidney in
U.S. ,ueterans, by age, type and amount smoked for current smokers
only

                1
                ,   Number of cigarettes smoked per day     Pipe
                                           and/or  Cigars
                  0     1-9    l&20   21-39 40 and             Pipe
                                           cigars
                                       over
                                __-      -1

Mortality ratios- _--_  1. 00   97   1. 34   1. 68 2. 75   1. 15   77   1. 32
Death rates:
  Age45-54_.._-_.__.._____.___..~..- _._--_ ---__- ~.._~..___._._____
  Age 55-64._----_    8     5
  Age 65-74__mm--_    14     7
  Age 75-W----    7 -_-._--_---- --_--_ ---__-

Somce: Kahn, IX. A. (46).

TABLE 4.-Mortality ratios and death rates for cancer of the kidney in
     male cigarette smokers, by speci$ed age groups

Cigarette smokers   -

Age 4564    Age 65-79
              -

Mortality ratios_--~.--~.~---~---~~--------~----~---     1. 42
Deathrates---_--- _.___._. --_---~_--_~---~.---.-___;   ' (416 ,     1. 57
                                      1 (15)23

1 Numbers in parentheses indicate death rates for persons who have never smoked regularly
SOURCE: Hammond, E. C. (S4).

105


Hammond (34) has also demonstrated higher mortality ratios in
cigarette smokers for cancer of the kidney.
Preliminary evidence from a &respective study in progress (It%)
suggests t.hat> cigarette smokers, espec.ially t.hose who smoke over 35
cigaret.tes a day, are over-represented in those patients with cancer of
the kidney. More research should be done t,o try to ascertain if there is
a meaningful relat,ionship between smoking and ca.ncer of the kidney.

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