Learning goals case 7
1. What are biomarkers and which types of biomarkers exist?
(BRON: Application of biomarkers in cancer epidemiology)
Biological marker = any substance, structure or process that can be measured in the human
body or its products and may influence or predict the incidence (new cases who get disease)
or outcome of disease (IARC 1997).
Types of biomarkers
- Molecular markers glucose levels for example
Exogenous compounds and their metabolites (nutrients, xenobiotics (other
compounds than nutrients that are not so necessary for our functioning) etc.),
they are coming from the outside. Such as Vitamin C via the diet.
Normal body constituents such as estrogen .
Endogenous compounds that are not present under normal conditions in a
healthy body, such as cytokines profiles.
Abnormalities of body chemistry, structure or function, such as mutations.
- Imaging brain scan
- Functional measurements blood pressure or an electrocardiogram
Use of biomarkers in cancer epidemiology
- To gain knowledge about the distribution and determinants of disease occurrence and
outcome that may be applied to reduce the frequency and impact of disease in human
population
- To increase the accuracy of measurements of genetic or other acquired susceptibility to
disease
- To increase the accuracy of measurements of exposures that may cause or prevent
disease
- To increase the accuracy of measurements of exposure that confound or modify the
associations between risk and other exposures
- To increase the accuracy of measurements of factors that may determine the outcome of
disease, such as disease precursors and stages
- May also be used to reduce, in the proposed study, the time interval between the
relevant exposure and measurement of the putative (vermeende) effect and to increase
the yield of information on disease pathogenesis.
- Serve to increase the cost-effectiveness of epidemiological studies, in the sense that, as a
result of their use, more information is gained per unit cost.
So, the advantages of biomarkers in short:
- Increase accuracy of measurement of:
o Genetic or other susceptibility to disease
o Exposures that cause or prevent disease
o Variables that confound or modify associations
o Disease
- Reduce time interval between exposure and disease shorter studies
- Increase information on disease pathogenesis
- Increase cost-effectiveness
,Three types of biomarkers
- Exposure
An exogenous substance or first metabolite that is measured in compartment within an
organism. These are indicators of current and/or past exposure. (for example measuring
plasma concentration of folic acid) for example nicotine in the blood from cigarettes.
- Effect / outcome
A measurable biochemical, physiological, behavioural or other alteration within an organism,
that can be recognized as associated with an established or possible health impairment or
disease. In short, these biomarkers reflect outcome and they are a result of interaction
between exposure and the exposed body.
- Susceptibility
An indicator of an inherent or acquired ability of an organism to respond to the challenge of
exposure to specific xenobiotic substance. So, they are indicator of likelihood of getting an
disease ones you are exposed.
The most well-known biomarkers in these category are genetic variance
(polymorphisms). Gene BRCA if you have polymorphism there , the gene is mutated
and your risk for breast cancer is 5 times higher.
Acquired susceptibility biomarkers, for example ones you had a stroke the change on
having a second one increased.
- Three outer circles; genetic factors, environment and disease
Represent the universe of phenomena that can be measured to reflect the amount or
effects of exogenous or endogenous agents that may influence or predict the incidence
or outcome of disease
- Inner circle; biomarkers
Represents the subset of these phenomena that can be measured in the human body.
, Biomarkers, more than any other epidemiological measure, may measure elements of
elements any two or three outer circles.
Application areas of biomarkers:
- Screening programmes for example a colon cancer screening programme, they send
around a small collection kit which the persons has to send back to the lab. If the test
was positive, people would be send to the hospital.
- Diagnosis diagnosis of a disease
- Monitoring treatment for example in bipolar disorder, people have to take lithium as
a drug. It is very import to monitor of the plasma levels of lithium in order to insure that
the drug levels are stable and that the patient doesn’t get an excess.
- Assessing exposure in a research setting for example environmental and dietary
exposures
- Monitor compliance actually check if someone takes a drug or if someone actually
eats a prescribed diet.
- Predicting changes of getting a disease for example genetic variance
You can use biomarkers in clinical practice and in research
Application of biomarkers in clinical practice important
- Early diagnosis biomarker as an indicator or surrogate endpoint, instead of waiting if
someone gets a disease you measure a biomarker that reflects the disease as a very early
stage (early diagnosis). An example is measuring cholesterol and determining the risk for
cardiovascular disease.
- Prognosis
- Study the effect of treatment
A very limited number of potential useful biomarkers is used because there are very
many legal requirements. Evidence have to be really solid if biomarkers have to be
allowed. Also, a biomarker has to be reliable at an individual level. It has to say
something about one specific patient a doctor is looking at. In the picture below you can
see all the legal requirements a biomarker has to fit in before it can be used in clinical
practice.
1. What are biomarkers and which types of biomarkers exist?
(BRON: Application of biomarkers in cancer epidemiology)
Biological marker = any substance, structure or process that can be measured in the human
body or its products and may influence or predict the incidence (new cases who get disease)
or outcome of disease (IARC 1997).
Types of biomarkers
- Molecular markers glucose levels for example
Exogenous compounds and their metabolites (nutrients, xenobiotics (other
compounds than nutrients that are not so necessary for our functioning) etc.),
they are coming from the outside. Such as Vitamin C via the diet.
Normal body constituents such as estrogen .
Endogenous compounds that are not present under normal conditions in a
healthy body, such as cytokines profiles.
Abnormalities of body chemistry, structure or function, such as mutations.
- Imaging brain scan
- Functional measurements blood pressure or an electrocardiogram
Use of biomarkers in cancer epidemiology
- To gain knowledge about the distribution and determinants of disease occurrence and
outcome that may be applied to reduce the frequency and impact of disease in human
population
- To increase the accuracy of measurements of genetic or other acquired susceptibility to
disease
- To increase the accuracy of measurements of exposures that may cause or prevent
disease
- To increase the accuracy of measurements of exposure that confound or modify the
associations between risk and other exposures
- To increase the accuracy of measurements of factors that may determine the outcome of
disease, such as disease precursors and stages
- May also be used to reduce, in the proposed study, the time interval between the
relevant exposure and measurement of the putative (vermeende) effect and to increase
the yield of information on disease pathogenesis.
- Serve to increase the cost-effectiveness of epidemiological studies, in the sense that, as a
result of their use, more information is gained per unit cost.
So, the advantages of biomarkers in short:
- Increase accuracy of measurement of:
o Genetic or other susceptibility to disease
o Exposures that cause or prevent disease
o Variables that confound or modify associations
o Disease
- Reduce time interval between exposure and disease shorter studies
- Increase information on disease pathogenesis
- Increase cost-effectiveness
,Three types of biomarkers
- Exposure
An exogenous substance or first metabolite that is measured in compartment within an
organism. These are indicators of current and/or past exposure. (for example measuring
plasma concentration of folic acid) for example nicotine in the blood from cigarettes.
- Effect / outcome
A measurable biochemical, physiological, behavioural or other alteration within an organism,
that can be recognized as associated with an established or possible health impairment or
disease. In short, these biomarkers reflect outcome and they are a result of interaction
between exposure and the exposed body.
- Susceptibility
An indicator of an inherent or acquired ability of an organism to respond to the challenge of
exposure to specific xenobiotic substance. So, they are indicator of likelihood of getting an
disease ones you are exposed.
The most well-known biomarkers in these category are genetic variance
(polymorphisms). Gene BRCA if you have polymorphism there , the gene is mutated
and your risk for breast cancer is 5 times higher.
Acquired susceptibility biomarkers, for example ones you had a stroke the change on
having a second one increased.
- Three outer circles; genetic factors, environment and disease
Represent the universe of phenomena that can be measured to reflect the amount or
effects of exogenous or endogenous agents that may influence or predict the incidence
or outcome of disease
- Inner circle; biomarkers
Represents the subset of these phenomena that can be measured in the human body.
, Biomarkers, more than any other epidemiological measure, may measure elements of
elements any two or three outer circles.
Application areas of biomarkers:
- Screening programmes for example a colon cancer screening programme, they send
around a small collection kit which the persons has to send back to the lab. If the test
was positive, people would be send to the hospital.
- Diagnosis diagnosis of a disease
- Monitoring treatment for example in bipolar disorder, people have to take lithium as
a drug. It is very import to monitor of the plasma levels of lithium in order to insure that
the drug levels are stable and that the patient doesn’t get an excess.
- Assessing exposure in a research setting for example environmental and dietary
exposures
- Monitor compliance actually check if someone takes a drug or if someone actually
eats a prescribed diet.
- Predicting changes of getting a disease for example genetic variance
You can use biomarkers in clinical practice and in research
Application of biomarkers in clinical practice important
- Early diagnosis biomarker as an indicator or surrogate endpoint, instead of waiting if
someone gets a disease you measure a biomarker that reflects the disease as a very early
stage (early diagnosis). An example is measuring cholesterol and determining the risk for
cardiovascular disease.
- Prognosis
- Study the effect of treatment
A very limited number of potential useful biomarkers is used because there are very
many legal requirements. Evidence have to be really solid if biomarkers have to be
allowed. Also, a biomarker has to be reliable at an individual level. It has to say
something about one specific patient a doctor is looking at. In the picture below you can
see all the legal requirements a biomarker has to fit in before it can be used in clinical
practice.
