Causal Inference in Cancer

Epidemiology

Crispin Kahesa
MD,MSc,PhD
Outline
• Introduction
• Concept of Cause
• Single and Multiple Causes
• Factors in Causation
• Interaction
• Guidelines for Causation
• Analysis and Interpretation of Causation
• Conclusion
Introduction
• Most of the cancer the cause is not Clear
• In pathogenesis of Cancer many factors inter play part
• A major goal of Cancer epidemiology is to assist in the prevention and
control of disease
• Prevention can only be achieved only after discovering the causes of
the disease
Concept of Cause
• An Understanding of the cause in Oncology is very important not only
for prevention but also in in diagnosis and the application of
treatment
• A cause of the disease is an event, condition, characteristics or
combination of these factors which play an important role in
producing the disease
• A cause could be sufficient or necessary
Sufficient Cause
• Cause is termed sufficient when it inevitably/certainly produces or
initiates a disese
• In Cancer it is not usually a single factor
• It often comprises several Components e.g Cigarete smoking is one of
the Component of the sufficient cause in the Lung Cancer
• In general , it is not necessary to identify all component of sufficient
cause before effective prevention can take place, since the removal of
one component may interfere with the action of the others and thus
prevent the disease
NECESSARY CUSE
• A cause is termed necessary if a disease cannot develop in its absence
• Each sufficient cause has a necessary cause as a component
Single and Multiple Causes
• Pasteur’s work on micro organism led to the formulation, first by
Henle and then by Koch, of the following rules for determining
weather a specific living organism causes a particular disease:
It Must be present in every disease case
Must be able to be Isolated and grown in pure Culture
Cause specific disease when inoculated in susceptible anima.
It must be recovered from the animal and identified.
Cancer is caused by More than one causal
mechanism, and every causal mechanism
involves the joint action of Multitude of the
component causes
Limitation
• Anthrax was the first disease demonstrated to meet these rules which
have proved useful with some other infections disease but for most
disease(both infections and non infections) Koch’s rule for
determining causation are in adequate.
The causative organism may disappear when the disease develops.
Certain micro-organism cannot(at present time) be grown in pure
culture
Not all organisms exposed to an infectious agent will acquire the
infection
Factors in Causation
• Four types of factors play a part the causation of disease.
All may be necessary but will rarely be sufficient to cause a disease
1. Predisposing Factors: Create a state of susceptibility to a disease agent. e.g. age,
sex, previous illness. These may have no direct bearing on the cause of the disease
but they aid other risk factors e.g. salivary gland diseases for caries development
2. Enabling Factors: Environmental conditions which favor the development of
disease.E.g Low income, poor housing, poor nutrition, in adequate medical facility
3. Precipitating factors: Specific or noxious agent, exposure to which can be
associated with the onset of a disease egg. Pollens in asthmatic attack, HIV in
cancer of the cervix
Reinforcing Factors: Factors which
aggravates an already established disease or
state e.g. repeated exposure and unduly hard
work
The term risk factors are those factors that
have direct link to the cause of the disease but
are not sufficient to cause the disease
Interaction
• The effect of two or more causes acting together is often greater than
would be expected on the basis of individual Effects
• Two or more causes acting together to amplify the intensity of the
effect produced
• Egg risk of cancer in smoker exposed to asbestos is greater than the
summation of the effect of each of the factors.
ESTABLISHING THE CAUSE OF A
DISEASE
• Causal inference is the term used for the process of determining
weather observed associations are likely to be causal; the use of
guidelines and making of judgements are involved.
• Before an association is assessed for possibility that it I s causal, other,
explanations such as chance, bias and confounding have to be
excluded
GUIDELINES FOR CAUSATION

• Bradford Hill (1965)

Temporal relation
Plausibility
Consistency
Strength
Dose relationship
Reversibility
Judging the evidence
Temporal Relationship
• Necessity for a cause to precede an effect in time
-this usually self-evident
Difficult to elicit in resection or case control study
Plausibility
• An association is plausible and more likely causal if consistent with
other knowledge
• Problem with plausibility; it is too often not based on logic or data,
but only on prior beliefs. Lack of which may be simple reflection of
medical knowledge.
Consistency
• Refers to the repeated observation of an association in different
populations under different circumstances obtained from different
studies.
• Lack of consistency, however, does not rule out a causal association,
because different exposures level and other conditions may reduce
the impact of the causal factor in other causes.
Strength
• Hills argument is that strong association between possible cause and
effect are more likely to be causal than weak associations
• The facts that an association is weak does not rule out a causal
connection. Passive smoking and Lung cancer
Dose relationship
• A dose-relationship occurs when changes in the level of a possible
cause are associated with changes in the prevalence or incidence
Reversibility
• When the removal of a possible cause results in a reduced disease
risk, the like hood of the association being causal is strengthened.
• Cessation of smoking reduces the risk of developing lung cancer
Judging the Evidence Evidence
• No Completely reliable means of establishing relationship and
sometime causal can be conflicting
• To make causal Inference all available evidence should be considered
The Knowledge of causation is an integral
part in cancer epidemiology as it enables us
to make proper dx,Formulate the correct
treatment plan and take necessary measures
in the prevention of cancer