world cancer report - iarc

MOLECULAR EPIDEMIOLOGY
In 1982, “molecular cancer epidemiology”
was defined as “an approach in which
advanced laboratory methods are used in
combination with analytic epidemiology to
identify at the biochemical or molecular
level specific exogenous and/or host factors
that play a role in human cancer causation”
(Perera FP, Weinstein IB, J Chron
Dis 35: 58l-600, 1982). Four categories of
biomarkers were described: internal dose,
biologically effective dose, response, and
susceptibility. The hope was that, by introducing
biomarkers into epidemiology,
researchers “should be able to predict
human risks more precisely than hitherto
possible”. Since then, molecular cancer
epidemiology has evolved rapidly, with
special programmes in many schools of
public health.
The stated goal of molecular cancer epidemiology
is the prevention of cancer.
Considerable molecular epidemiologic
research has focused on environmental
causes because many lines of evidence
indicate that the factors that determine
the great majority of cancers incidence
are largely exogenous and hence preventable
(Lichenstein P et al., N Engl J Med
343: 78-85, 2000). These include exposures
related to lifestyle and occupation,
and pollutants in air, water, and the food
supply. This awareness has lent greater
urgency to the search for more powerful
tools in the form of early-warning systems
to identify causal environmental agents
and flag risks well before the malignant
process is entrenched.
other organochlorine pesticides cause
liver cancer in rats. DDT in particular
has been associated with increased risk
of pancreatic cancer, breast cancer,
lymphoma and leukaemia in humans.
Some organochlorines exhibit sex
steroid activity in relevant assay systems,
and these pesticides are consid-
EXPOSURE
ASSESSMENT MARKERS OF DOSE
EARLY DETECTION & CLINICAL
POPULATION
STATISTICS
TO HUMANS
PROGNOSTIC MARKERS DISEASE
Environmental
or
endogenous
agents
Absorption
Distribution
Metabolism
Metabolites
in body fluid
& excreta
Potential molecular endpoints (specified in the lower section) that may serve as the basis for molecular epidemiological
studies. These endpoints may be indicative of biological processes contributing to cancer development
as shown in the upper section.
The potential contribution of molecular epidemiology
includes: providing evidence
that environmental agents pose carcinogenic
risks, helping establish the causal
roles of environmental factors in cancer,
identifying environment-susceptibility
interactions and populations at greatest
risk and developing new intervention
strategies. A recent review of the field
(Perera F, J Natl Cancer Inst, 92: 602-612,
2000) critically evaluated the progress to
date using as illustration research on
tobacco smoke, polycyclic aromatic hydrocarbons,
aflatoxin B 1, benzene and hepatitis
B virus and their role in lung, breast,
liver cancer and leukaemia. It concluded
ered to have the potential to disrupt
endocrine-regulated homeostasis.
Attempts have been made to correlate
levels of organochlorines and polychlorinated
biphenyls in breast tissue with
breast cancer risk in several communities,
but without clear-cut results [8].
For the major pesticides, international
PRIMARY PREVENTION AND CLINICAL INTERVENTIONS
DNA adducts,
protein adducts
Repair
Replication
Mutation in
reporter genes,
oncogenes,
supressor genes
SUSCEPTIBILITY FACTORS
genetic/environmental
Cell proliferation
Clonal expansion
Genomic
instability,
abberrant gene
expression,
altered
cell structure
Further
genetic
change
Malignant
tumour
that molecular epidemiology has identified
a number of carcinogenic hazards, in
some cases providing definitive etiologic
data, furthering our understanding of individual
genetic and acquired susceptibility
to environmental carcinogens. However,
molecular epidemiology has not yet led to
broad policy changes to prevent or to
reduce exposure to carcinogens. What is
now needed is timely translation of existing
data into risk assessment and public
health policy as well as focused research
to fill gaps in scientific knowledge.
regulations exist with regard to permissible
amounts of residues in foods – the
ADI, or acceptable daily intake, being
the primary reference level for such
exposures. ADI levels are determined by
expert groups convened by WHO, and
published as the WHO Pesticide Residue
Series.
Food contaminants 45