1 History
Oesophageal cancer was rare in East, Central and Southern Africa until the 1930s.
Its incidence has risen rapidly since then to make it one of the commonest cancers
in the region, and in some areas the leading cause of death.
2 Squamous cancer in non-endemic areas
Tobacco and alcohol are the two constant associations with SCO worldwide in low and
medium incidence areas. Each has a linear, dose-related effect. Using both alcohol
and tobacco has a synergistic effect. Specific predisposing conditions in low and
medium incidence countries have in common a reduction in oesophageal exposure to
acid; some also involve reflux.
3 Disease description
Cancer of the Oesophagus (Esophagus) in Africa presents usually with dysphagia for
fluids, weight loss and dehydration. 97% is squamous. It occurs predominantly in
the middle third of the Oesophagus (Esophagus). Both late presentation and limited
medical facilities dictate that treatment is normally palliative and survival normally
brief.
4 Incidence
In most countries of the world the annual incidence rate of oesophageal cancer is
less than 10 per 100,000 people. Males predominate. Three areas of the world have
very high incidences: Linxian province in China, The Caspian Littoral region, and
Transkei in South Africa. The highest reported incidence is 547.2 per 100,000 males
aged 35-64 in Kazakhstan on the Caspian Littoral. Throughout East, Central and Southern
Africa there is a high incidence . Unlike other high incidence areas of the world,
Africa’s high incidence has arisen in the last century, from a negligible start.
Dramatic differences in incidence exist over short distances.
5 Who gets SCO?
In Africa, the most susceptible population is rural, involved in subsistence farming
of poor land. Their chief crop and chief food is maize. They are poor but with some
education and some cash income. There is no ethnic pattern. In rural Transkei, an
endemic area, there is a marked abnormality of upper gastrointestinal function including
gastric acid suppression, heartburn, and reflux.
6 Case-Control Studies
Case-control studies all confirm that the most susceptible group is rural or has
a rural base, and is transitional in terms of culture and education; the group is
of low education and socio-economic status. There is a strong association with tobacco
usage, but not with alcohol in close case-controlled studies in endemic areas. The
most susceptible population has a traditional diet of maize, pumpkin and beans. There
is a strong and dose-related association with use of maize meal. A high-level association
with Solanum nigrum was found in one study.
7 Environmental studies
The environment indirectly affects foods of subsistence farmers. There is no proven
direct association between environment and SCO.
8 Foods I – Maize
Maize has a consistent and genuine association with SCO, but its history in Africa
is much longer than that of SCO. It has steadily taken over from other staples throughout
much of East, Central and Southern Africa. Maize meal is the form of maize most strongly
linked to SCO, has the greatest deficiencies and the greatest degenerative chemical
change; there is a dose-related effect and a high relative risk. In the middle of
the twentieth century, the sudden rise in oesophageal cancer was paralleled by a
rise in the use of maize, a change to white dent maize, and easy availability of
commercially milled maize to rural people .
9 Maize, linoleic acid and prostaglandin E2
A maize-based, otherwise poor diet has a very high omega-6 to omega-3 fatty acid
ratio, and because of this increases PGE2 production throughout the body, including
the gastric mucosa. Linoleic acid in esterified form mediates a slow sustained production
of PGE2. Nonesterified linoleic acid causes a rapid and temporary increase of PGE2
production in the gastric mucosa. There are significant effects of intragastric PGE2
on upper GI function including acid suppression and upper GI reflux. These same effects
are produced by maize consumption; the slow effects by a maize-based diet, the rapid
effects by maize meal. PGE2 is also directly mitogenic to the oesophageal mucosa.
10 Foods II – other foods
Alcohol is not a risk factor in endemic areas for SCO. Vitamins and mineral supplements
have usually been given in multiples. The one micronutrient that passes the tests
of proven deficiency in endemic areas - significant lower levels in SCO victims,
and significant improvement on supplement is deficiency of selenium. Lower level
evidence exists against deficiencies of riboflavin, vitamin E and beta-carotene.
Solanum nigrum and lima beans have evidence of a positive association with SCO from
a single case-control trial only, but both have the possibility of being major aetiological
factors since they have highly significant associations. Pumpkin also has scanty
evidence against it except as part of the Transkei diet of maize, pumpkin and beans,
but a significant association may be present. The protective value of dietary fat
is strongly supported by two case-control studies in very high risk areas. Fresh
fruit and vegetables have evidence of a protective effect worldwide, but inconsistent
evidence in high-risk areas.
11 Carcinogens
No single potent carcinogen has been found on which the endemic incidence of SCO
can be blamed. There is good evidence that no such undiscovered potent carcinogen
exists. Tobacco is an important carcinogen in Africa with a dose and time-related
effect. In the absence of tobacco there would still be a very high incidence of SCO
in endemic areas. Human papillomavirus is associated in a minority of cancers, and
this may be a causal association. Nitrosamines are found in the environment but not
at such a level that they could explain the very high incidences found. Plant mycotoxins
are present in the environment and the evidence would support a minor role in the
carcinogenic process: fumonisin B1 is not a proven carcinogen for the human Oesophagus
(Esophagus) in the amounts so far demonstrated in Africa. The pattern of genetic
damage in endemic areas is different from those in areas where the disease is more
sporadic.
12 Reflux
Duodenal fluid reflux into the Oesophagus (Esophagus) is carcinogenic. Duodenal reflux
without gastric content is significantly more powerfully carcinogenic. The evidence
supports gastric acid as being a protective factor. In humans, conditions which are
associated with reflux and acid suppression including pernicious anaemia, gastrectomy
and alcohol consumption, are also associated with squamous carcinoma.
13 What causes oesophageal cancer?
High level and consistent evidence exists to associate SCO with maize as the monostaple,
the diet of maize pumpkin and beans, maize meal consumption, tobacco, and low dietary
fat intake. Lower level but consistent evidence supports a link with human papillomavirus,
and deficiencies of vitamin and selenium intake. Pumpkin, beans and Solanum nigrum
have high-level but inadequately corroborated evidence implicating them. Other agents
including fumonisins, nitrosamines, traditional beer and alcohol have had adequate
research and have no convincing evidence against them. The evidence points to diet
as the base for endemic incidences of the disease. A high maize meal intake, poverty
of dietary fat and dietary deficiencies including selenium are the best evidenced
associations. The history of the availability of commercially milled maize and the
time-scale of the ‘epidemic’ are compatible with a causal association.
14 A proposed aetiology of ESCO
Maize meal, a low-fat diet, and other microdeficiencies including selenium, together
create an excess production of PGE2 in the stomach. Excess PGE2 causes inhibition
of gastric acid production, and duodeno-gastro-oesophageal reflux. These physiological
abnormalities are carcinogenic. Each of these steps is evidenced in theory. Each
step has good corroborating evidence in high-risk and endemic areas of Africa. This
aetiological chain provides an explanation for the high incidence of the disease
in certain areas, its timescale, apparent spread, the lack of influence of alcohol
in endemic areas, and the targeting of the rural transitional population. Other factors
which boost the incidence of SCO in certain communities and individuals include tobacco,
HPV, pumpkin and beans, and may also include Solanum nigrum.
15 Preventative actions
On the basis of already broadly accepted ideas of causation, health education to
ensure a variety of diet, and education about the very high danger of tobacco in
the endemic situation are all justified, but not likely to be immediately or highly
successful.The most logical education message is that added dietary fat is preventative.
Stabilisation treatment of maize meal and strict distribution and storage conditions
may be both effective and achievable. Omega-3 fatty acid supplementation of maize
meal, if possible in cost and taste terms, is an alternative which would at the same
time make a good contribution to general health. For the generations already long-exposed
to the endemic base factors, strict avoidance of carcinogens may be the only preventative
option.
