THE CANCER PROBLEM Almost all cancers appear to be caused by exposure
to
factors
in the environment. The most promising approach to the control of the disease is to identify those factors and eliminate them
by John Cairns
D
uring the past 150 years the West
thought of as an unpredictable disease
organ in which they originate and by the
ern world has virtually elimi
that strikes indiscriminately at rich and
kind of cell involved. When they are
nated infectious diseases as a sig
poor, fat and thin, old and middle-aged,
considered in this way, there are 100
nificant cause of death. A child born in
as if it usually owed nothing to external
or so distinct varieties of the disease.
the U.S. today can look forward to a life
causes. If that were true, our only hope
Such an elaborate classification would be
untroubled by fear of diseases such as
of overcoming cancer would be to im
of no general interest were it not that the
scarlet fever, diphtheria, tuberculosis,
prove the treatment of the disease. One
different varieties plainly have different
typhoid fever and dysentery, which were
object of this article is to show that most
causes, since the incidence of each one changes independently when the en
major causes of death three or four gen
of the common kinds of cancer seem to
erations ago. Life expectancy has been
be caused in large part by environmen
vironment is altered. Most of the 100
increasing steadily since the middle of
tal factors; because we can act to alter
varieties are rare, and so we can account
the 19th century. The longer average life
the envIronment, those cancers are po
for most cancer mortality by considering
span is a result mainly of improvements
tentially avoidable.
a fairly short list of diseases. Roughly half of all cancer deaths are
in public health; the more spectacular fruits of scientific research, such as the introduction of vaccines and antibiotics, merely completed the process.
Incidence Groups of abnormally proliferating
caused by cancers of three organs: the lung, the large intestine and the breast
[see illustration on page 66].
There can
cells can arise in any part of the body.
therefore be no major inroad on overall
to old age and can therefore be attrib
Those that cannot invade the surround
cancer mortality until some means are
uted to diseases that are either peculiar
ing tissues and so remain strictly local
found for curing or preventing these
to old age or lethal only in old people.
growths are called benign tumors. Those
three kinds of cancer. Each of them can
Although innumerable changes in the
that spread from their site of origin and
be considered a discrete entity because
Death has now been confined mostly
body that accompany advancing age
can therefore reach the bloodstream and
the frequency of each varies indepen
could be classified as diseases, two par
the lymphatic system are called malig
dently when factors in the environment
ticular conditions commonly arising in
nant tumors, or cancers.
are changed.
old age are often a direct cause of death:
The cancers are divided into three
It could reasonably be argued that we
arterial disease (atheroma and arterio
broad groups. The carcinomas arise in
are not interested in total numbers of
sclerosis) and cancer. Arterial disease is
the epithelia, the sheets of cells covering
deaths as much as in loss of life span.
lethal when it affects the arteries supply
the surface of the body and lining the
The death of a 90-year-old man from
ing the heart or the brain; it now ac
various glands. The much rarer sarcomas
cancer of the prostate is less of a tragedy
counts for about 50 percent of all deaths
arise in supporting structures such as
than the death of a young man from leukemia. In determining our priorities
in the U. S. Cancers are lethal when they
fibrous tissue and blood vessels. The leu
spread from their site of origin; they now
kemias and lymphomas arise in the
we should therefore take into considera
account for almost 20 percent of all U.S.
blood-forming cells of the bone marrow
tion the age distribution of the victims
and lymph nodes. These three words
of each cause of death. There are vari
deaths. People have very different attitudes
carcinoma, sarcoma and leukemia-are
ous ways of doing this. For example, it is
toward these two diseases. It is not just
so entrenched in everyday usage that
possible to calculate how much each ma
that death from arterial disease is often
they must be mentioned, but I do not
jor cause of death or each kind of cancer
rapid, whereas death from cancer can be
mean to imply by their use that there are
diminishes the average life expectancy
painfully drawn out. For some reason
three basically different forms of carcino
or, in particular, how much each reduces
heart attacks and strokes tend to be
genesis or that the three kinds of cancer
our working life up to the age of 65. The main effect of such a weighting proce
thought of as natural hazards of age, and
have different prospects for prevention
either a normal end to a satisfactorily
and cure. That kind of information can
dure is to increase the relative impor
long life or, when they occur in middle
be obtained only through a finer system
tance of accidents among the general
aged men, the wages of overeating and
of classification.
causes of death, and of the leukemias
lack of exercise. In contrast, cancer is
Cancers are classified mainly by the
64 © 1975 SCIENTIFIC AMERICAN, INC
and lymphomas among the cancers. Can-
GROWTH OF A TUMOR in the breast ordinarily threatens life
tissue in which it develops. A cancerous tumor (bottom) can spread
only when the tumor can spread to distant parts of the body. The
throughout the glandular tissue, can often involve ligaments and
normal breast (top) is organized into glandular tissue, fat and other
skin and can sometimes penetrate the muscle underlying the breast.
structures. Tumors arise almost exclusively in the glandular tissue;
In addition cancers can in some cases migrate through the blood or
they are composed of cells in which the normal restraints on growth
the lymphatic system to establish new colonies of cells in distant,
and reproduction have been removed. A benign tumor (middle)
unrelated organs. This is the process known as metastasis. It is the
can grow rapidly and become quite large, but it cannot escape the
metastatic spread of cancers that is responsible for their lethality.
·65 © 1975 SCIENTIFIC AMERICAN, INC
1 00
cer of the lung, however, still remains at the top of the list. All these statistics refer to mortality,
LUN G
LUN G 90
287,000
65,000
-
ACCIDENTS
and that is the most accessible and re liable measure of the impact of cancer. Estimating the incidence of the different cancers is not as easy. To begin with, one
2,346,000
might consider the patients who present themselves to a physician and are found to have cancer. Most of them will sooner 80
or later die of their cancer; this single
-
BREAST ARTERIAL DISEASES 874,000
208,000
depressing statistic reinforces the point that science has had little impact on dis eases that mainly affect the middle-aged
LARGE INTESTIN E
and the old. An alternative definition of
46,000
incidence would include not only those 70
cancers that have begun to cause symp
-
LEUKEMIA 176,000
BREAST 30,000 60
ARTERIAL DISEASES
cancer have been sought in this way by
2,027,000
-
routine surveys, and it has become plain LARGE I NTESTIN E 14 1 ,000
PANCREAS
can be detected than might have been expected. It follows that most of those either regress before they become very
-
CANCE R 336,000
PROSTATE
BRAIN
17,000
117,000
STOMACH 1 6,000
conventional estimate of the incidence
1,684,000
LYMPHOMA 114,000
of cancer of the prostate in 70-year-old men is about 200 cases per 100,000 men per year, or .2 percent per year; routine
14,000
-
large or, more likely, grow so slowly that they do not give rise to symptoms during the patient's lifetime. For example, the
CANCER
LEUKEMIA 40
that far more small, symptomless cancers
minute collections of invasive cells must
18,000 t Z UJ II 50 a: UJ a..
toms but also those that can be detected by a deliberate search. Many kinds of
autopsies of 70-year-old men who had ACCIDENTS
RESPIRATOR) DISEASES
1 1 5,000
459,000
died of other causes, however, have shown microscopic invasive cancers of the prostate in from 15 to 20 percent of them. The incidence measured by this
HOMICIDE 30 -
401 ,000
RESPIRATOR) DISEASES
method is thus 100 times as great. When the site of the cancer is acces
SUICIDE
1 1 3,000
sible to direct examination, surveys are
390,000
much easier to carry out; they give the 20
OTHER CANCERS
OTHER CAN CERS
-
701,000
1 30,000
same result. For example, a recent sur vey in a rural
district of Tennessee
showed that about 4 percent of the adult
population have skin cancer. Indeed, it OTHER CAUSES OF DEATH 10
-
490,000
OTHER CAUSES OF DEATH 2,363,000
seems likely that if we could extend such a detailed examination to the entire body we would find that by middle age each of us has acquired several nests of pro liferating, invasive cells that might rea sonably be classified as cancers. Without knowing much more about the natural history of the disease we cannot predict
o
which of these cancers will spread and NUMBER OF DEATHS (ANNUAL TOTALS)
LOSS OF WORKING LIFE (ANNUAL MAN YEARS LOST)
DEATHS FROM CANCER now make up almost a fifth of all deaths in the U.S. Of the
deaths that are attributed to cancer, more than 60 percent are caused by a few common forms of the disease. The remainder are distributed among more than 100 other cancers. The
impact of each kind of cancer can also be judged from the loss of life span it causes, measured here in lost working years, with working life assumed to extend from age 20 to age 65. Among
which will not. Before discussing the natural history of cancer, however, I should like to consider what can be de duced about the causes of the disease by studying its epidemiology. The first step in finding out what causes any particular variety of cancer
all causes of death, the principal effect of considering loss of life span instead of simple mor
is to determine which groups of people
tality is to increase the importance of accidents; among cancers, it emphasizes relatively
show the highest incidence and what
high incidence of leukemias in young people. Lung cancer, however, is still predominant.
distinguishes them from other people.
66 © 1975 SCIENTIFIC AMERICAN, INC
Those most conspicuously at risk are of
f-..-.--...-..-.....-..... ....-.--+--� �--r-----+----+----+---t-----l
course the old. Almost all kinds of can cer are much commoner in old people,
..._.._ .._..-.. -_.....
--.-...-�--f- �-.-+�--+�---!�--t ..
and the incidence rises steeply with age. To take a typical example, the death rate from cancer of the large intestine in creases about a thousandfold between the ages of 20 and 80, and most of the increase comes after age 60
tion at right J.
[see illustra
Model of Carcinogenesis Various models have been proposed to account for the clustering of cancer in old age. One of the most reasonable models postulates that each cell has sev eral genes that independently restrain it from forming a cancer, so that it will not form one until each of those genes has been inactivated by mutation. Because mutations can be introduced at any time in the life of a cell or of its ancestors, the probability that any one of our cells has a mutation in a particular gene increases in direct proportion to our age. The probability that the cell has mutations in all
n
of its
n
..
100
restraining genes (and is
thus cancerous) therefore rises as the nth power of our age. The risk of having cancer should therefore increase as the nth power of our age; expressed another way, the logarithm of cancer incidence
z 0 F=
:5
--
::J 0.. 0 0.. Z 0 :J :! :::?:
ex: w !!:.. w f
to
factors
in the environment. The most promising approach to the control of the disease is to identify those factors and eliminate them
by John Cairns
D
uring the past 150 years the West
thought of as an unpredictable disease
organ in which they originate and by the
ern world has virtually elimi
that strikes indiscriminately at rich and
kind of cell involved. When they are
nated infectious diseases as a sig
poor, fat and thin, old and middle-aged,
considered in this way, there are 100
nificant cause of death. A child born in
as if it usually owed nothing to external
or so distinct varieties of the disease.
the U.S. today can look forward to a life
causes. If that were true, our only hope
Such an elaborate classification would be
untroubled by fear of diseases such as
of overcoming cancer would be to im
of no general interest were it not that the
scarlet fever, diphtheria, tuberculosis,
prove the treatment of the disease. One
different varieties plainly have different
typhoid fever and dysentery, which were
object of this article is to show that most
causes, since the incidence of each one changes independently when the en
major causes of death three or four gen
of the common kinds of cancer seem to
erations ago. Life expectancy has been
be caused in large part by environmen
vironment is altered. Most of the 100
increasing steadily since the middle of
tal factors; because we can act to alter
varieties are rare, and so we can account
the 19th century. The longer average life
the envIronment, those cancers are po
for most cancer mortality by considering
span is a result mainly of improvements
tentially avoidable.
a fairly short list of diseases. Roughly half of all cancer deaths are
in public health; the more spectacular fruits of scientific research, such as the introduction of vaccines and antibiotics, merely completed the process.
Incidence Groups of abnormally proliferating
caused by cancers of three organs: the lung, the large intestine and the breast
[see illustration on page 66].
There can
cells can arise in any part of the body.
therefore be no major inroad on overall
to old age and can therefore be attrib
Those that cannot invade the surround
cancer mortality until some means are
uted to diseases that are either peculiar
ing tissues and so remain strictly local
found for curing or preventing these
to old age or lethal only in old people.
growths are called benign tumors. Those
three kinds of cancer. Each of them can
Although innumerable changes in the
that spread from their site of origin and
be considered a discrete entity because
Death has now been confined mostly
body that accompany advancing age
can therefore reach the bloodstream and
the frequency of each varies indepen
could be classified as diseases, two par
the lymphatic system are called malig
dently when factors in the environment
ticular conditions commonly arising in
nant tumors, or cancers.
are changed.
old age are often a direct cause of death:
The cancers are divided into three
It could reasonably be argued that we
arterial disease (atheroma and arterio
broad groups. The carcinomas arise in
are not interested in total numbers of
sclerosis) and cancer. Arterial disease is
the epithelia, the sheets of cells covering
deaths as much as in loss of life span.
lethal when it affects the arteries supply
the surface of the body and lining the
The death of a 90-year-old man from
ing the heart or the brain; it now ac
various glands. The much rarer sarcomas
cancer of the prostate is less of a tragedy
counts for about 50 percent of all deaths
arise in supporting structures such as
than the death of a young man from leukemia. In determining our priorities
in the U. S. Cancers are lethal when they
fibrous tissue and blood vessels. The leu
spread from their site of origin; they now
kemias and lymphomas arise in the
we should therefore take into considera
account for almost 20 percent of all U.S.
blood-forming cells of the bone marrow
tion the age distribution of the victims
and lymph nodes. These three words
of each cause of death. There are vari
deaths. People have very different attitudes
carcinoma, sarcoma and leukemia-are
ous ways of doing this. For example, it is
toward these two diseases. It is not just
so entrenched in everyday usage that
possible to calculate how much each ma
that death from arterial disease is often
they must be mentioned, but I do not
jor cause of death or each kind of cancer
rapid, whereas death from cancer can be
mean to imply by their use that there are
diminishes the average life expectancy
painfully drawn out. For some reason
three basically different forms of carcino
or, in particular, how much each reduces
heart attacks and strokes tend to be
genesis or that the three kinds of cancer
our working life up to the age of 65. The main effect of such a weighting proce
thought of as natural hazards of age, and
have different prospects for prevention
either a normal end to a satisfactorily
and cure. That kind of information can
dure is to increase the relative impor
long life or, when they occur in middle
be obtained only through a finer system
tance of accidents among the general
aged men, the wages of overeating and
of classification.
causes of death, and of the leukemias
lack of exercise. In contrast, cancer is
Cancers are classified mainly by the
64 © 1975 SCIENTIFIC AMERICAN, INC
and lymphomas among the cancers. Can-
GROWTH OF A TUMOR in the breast ordinarily threatens life
tissue in which it develops. A cancerous tumor (bottom) can spread
only when the tumor can spread to distant parts of the body. The
throughout the glandular tissue, can often involve ligaments and
normal breast (top) is organized into glandular tissue, fat and other
skin and can sometimes penetrate the muscle underlying the breast.
structures. Tumors arise almost exclusively in the glandular tissue;
In addition cancers can in some cases migrate through the blood or
they are composed of cells in which the normal restraints on growth
the lymphatic system to establish new colonies of cells in distant,
and reproduction have been removed. A benign tumor (middle)
unrelated organs. This is the process known as metastasis. It is the
can grow rapidly and become quite large, but it cannot escape the
metastatic spread of cancers that is responsible for their lethality.
·65 © 1975 SCIENTIFIC AMERICAN, INC
1 00
cer of the lung, however, still remains at the top of the list. All these statistics refer to mortality,
LUN G
LUN G 90
287,000
65,000
-
ACCIDENTS
and that is the most accessible and re liable measure of the impact of cancer. Estimating the incidence of the different cancers is not as easy. To begin with, one
2,346,000
might consider the patients who present themselves to a physician and are found to have cancer. Most of them will sooner 80
or later die of their cancer; this single
-
BREAST ARTERIAL DISEASES 874,000
208,000
depressing statistic reinforces the point that science has had little impact on dis eases that mainly affect the middle-aged
LARGE INTESTIN E
and the old. An alternative definition of
46,000
incidence would include not only those 70
cancers that have begun to cause symp
-
LEUKEMIA 176,000
BREAST 30,000 60
ARTERIAL DISEASES
cancer have been sought in this way by
2,027,000
-
routine surveys, and it has become plain LARGE I NTESTIN E 14 1 ,000
PANCREAS
can be detected than might have been expected. It follows that most of those either regress before they become very
-
CANCE R 336,000
PROSTATE
BRAIN
17,000
117,000
STOMACH 1 6,000
conventional estimate of the incidence
1,684,000
LYMPHOMA 114,000
of cancer of the prostate in 70-year-old men is about 200 cases per 100,000 men per year, or .2 percent per year; routine
14,000
-
large or, more likely, grow so slowly that they do not give rise to symptoms during the patient's lifetime. For example, the
CANCER
LEUKEMIA 40
that far more small, symptomless cancers
minute collections of invasive cells must
18,000 t Z UJ II 50 a: UJ a..
toms but also those that can be detected by a deliberate search. Many kinds of
autopsies of 70-year-old men who had ACCIDENTS
RESPIRATOR) DISEASES
1 1 5,000
459,000
died of other causes, however, have shown microscopic invasive cancers of the prostate in from 15 to 20 percent of them. The incidence measured by this
HOMICIDE 30 -
401 ,000
RESPIRATOR) DISEASES
method is thus 100 times as great. When the site of the cancer is acces
SUICIDE
1 1 3,000
sible to direct examination, surveys are
390,000
much easier to carry out; they give the 20
OTHER CANCERS
OTHER CAN CERS
-
701,000
1 30,000
same result. For example, a recent sur vey in a rural
district of Tennessee
showed that about 4 percent of the adult
population have skin cancer. Indeed, it OTHER CAUSES OF DEATH 10
-
490,000
OTHER CAUSES OF DEATH 2,363,000
seems likely that if we could extend such a detailed examination to the entire body we would find that by middle age each of us has acquired several nests of pro liferating, invasive cells that might rea sonably be classified as cancers. Without knowing much more about the natural history of the disease we cannot predict
o
which of these cancers will spread and NUMBER OF DEATHS (ANNUAL TOTALS)
LOSS OF WORKING LIFE (ANNUAL MAN YEARS LOST)
DEATHS FROM CANCER now make up almost a fifth of all deaths in the U.S. Of the
deaths that are attributed to cancer, more than 60 percent are caused by a few common forms of the disease. The remainder are distributed among more than 100 other cancers. The
impact of each kind of cancer can also be judged from the loss of life span it causes, measured here in lost working years, with working life assumed to extend from age 20 to age 65. Among
which will not. Before discussing the natural history of cancer, however, I should like to consider what can be de duced about the causes of the disease by studying its epidemiology. The first step in finding out what causes any particular variety of cancer
all causes of death, the principal effect of considering loss of life span instead of simple mor
is to determine which groups of people
tality is to increase the importance of accidents; among cancers, it emphasizes relatively
show the highest incidence and what
high incidence of leukemias in young people. Lung cancer, however, is still predominant.
distinguishes them from other people.
66 © 1975 SCIENTIFIC AMERICAN, INC
Those most conspicuously at risk are of
f-..-.--...-..-.....-..... ....-.--+--� �--r-----+----+----+---t-----l
course the old. Almost all kinds of can cer are much commoner in old people,
..._.._ .._..-.. -_.....
--.-...-�--f- �-.-+�--+�---!�--t ..
and the incidence rises steeply with age. To take a typical example, the death rate from cancer of the large intestine in creases about a thousandfold between the ages of 20 and 80, and most of the increase comes after age 60
tion at right J.
[see illustra
Model of Carcinogenesis Various models have been proposed to account for the clustering of cancer in old age. One of the most reasonable models postulates that each cell has sev eral genes that independently restrain it from forming a cancer, so that it will not form one until each of those genes has been inactivated by mutation. Because mutations can be introduced at any time in the life of a cell or of its ancestors, the probability that any one of our cells has a mutation in a particular gene increases in direct proportion to our age. The probability that the cell has mutations in all
n
of its
n
..
100
restraining genes (and is
thus cancerous) therefore rises as the nth power of our age. The risk of having cancer should therefore increase as the nth power of our age; expressed another way, the logarithm of cancer incidence
z 0 F=
:5
--
::J 0.. 0 0.. Z 0 :J :! :::?:
ex: w !!:.. w f
