world cancer report - iarc

CHEMOPREVENTION
SUMMARY
> Chemoprevention is defined as reduction
of the risk of cancer development
through the use of pharmaceuticals or
micronutrients.
> The breast cancer drug tamoxifen
reduces the risk of developing a second
cancer in the other breast.
> A lower risk of colon cancer has been
observed following regular use of aspirin
and related non-steroidal anti-inflammatory
drugs which reduce the risk of recurrence
of adenomas.
> Trials to establish chemopreventive
activity by micronutrients, including
carotenoids and retinoids, among people
at high risk, have been inconclusive.
The goal of chemoprevention is to prevent
or reverse the process of carcinogenesis,
or to enhance regression of
abnormal cells or tissue to normality
with minimal or no side-effects. Relevant
mechanisms vary, and in many cases
have not been determined. Although the
carcinogenic process is often characterized
as being dependent on mutation,
epigenetic changes are also involved.
These may be perturbed during the 20year
(or longer) latent period before invasion
and metastasis occur (Multistage
carcinogenesis, p84) and appear to provide
the basis for chemopreventive activity
by a variety of agents. Chemoprevention
may have great potential for
control of cancer.
The scope of chemopreventive agents
Many studies have shown that people
who consume more vegetables and fruit
than persons at otherwise the same risk
who consume less or none, have a
reduced risk of cancer (Diet and nutri-
tion, p62). Although the results of intervention
trials of dietary augmentation
with fibre and fruit and vegetables to
reduce the occurrence of colonic polyps
have so far been negative, there is considerable
evidence, particularly from
experimental studies, that some chemicals
present in the diet at low concentrations
play an important role in protecting
against cancer. Some examples
include folate, curcumin, genistein, selenium
and tea catechins. Micronutrients
(defined as nutrients present in the body
in amounts less than 0.005% of body
weight) which appear to protect against
cancer include β-carotene, α-tocopherol
and ascorbic acid. The preventive activity
of vegetables and fruit is partially
credited to micronutrients. However,
intake of these agents as vitamin pills or
diet supplements is yet to be established
(through trials) as preventing cancer in
humans. So, although the evidence suggests
that modification of diet can lower
cancer risk, the same effect is not yet
Platelets
Endothelium
Stomach
Kidney
Thrombotaxane A 2
PHYSIOLOGICAL
STIMULUS
COX-1
Constitutive
Prostaglandin I 2
‘HOUSEKEEPING’
Prostaglandin E 2
achievable using easy-to-take, pre-packaged
natural or synthetic compounds.
Putative chemopreventive agents include
pharmaceutical drugs and hormonally
active agents. There is conclusive evidence
that tamoxifen reduces the risk for
contralateral breast cancer in women with
a previous diagnosis of breast cancer.
Observational studies indicate a moderately
reduced risk for colorectal cancer in
people using aspirin regularly, and an indication
of greater reduction in risk with
Fig. 4.25 The aim of chemoprevention is to prevent
cancer by the administration of easy-to-take,
pre-packaged natural or synthetic compounds typically
in the form of a pill.
Prostaglandin I 2
INFLAMMATORY
STIMULUS
COX-2
Inducible
INFLAMMATION
Prostaglandin E 2
Macrophages
Leukocytes
Fibroblasts
Colon neoplasia
Fig. 4.26 COX-1 and COX-2 cyclooxygenases: COX-1 is constitutively expressed and regulates the homeostasis
of various tissues, including the generation of cytoprotective prostaglandins. Inflammatory stimuli
induce COX-2, which is also highly expressed in colorectal neoplasia in the absence of stimulation.
Chemoprevention 151