MOLECULAR EPIDEMIOLOGY

Santoshi Poudel
MPH 2023
BPKIHS, Dharan, Nepal
 TABLE OF CONTENTS
About the book
Emergence of molecular epidemiology
Goals of Molecular Epidemiology
Why Molecular Epidemiology
Traditional Vs molecular epidemiology
Molecular Vs Genetic Epidemiology
Uses of molecular epidemiology
Study design
Cancer Epidemiology
Molecular Epidemiology Tools 2
 ABOUT THE BOOK
Book Title: MOLECULAR EPIDEMIOLOGY OF CHRONIC DISEASES

Editors: Chirs Wild (University of Leeds,

UK)
Paolo Vineis ( Imperial college,
London UK)
Seymour Garte (University of
Pittsburgh PA, USA)
Publications: John Wiley and sons, Ltd
Publication year: 2008
Total chapter: 26

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 EMERGENCE OF MOLECULAR
EPIDEMIOLOGY

• Epidemiology identifies factors influencing disease risk, aiding prevention strategies.

• Molecular epidemiology, integrating molecular techniques, offers new insights.

• Molecular epidemiologists are searching for genes of individuals that interact with
environment and lifestyle factors such that cancer risk is not equally elevated in all
persons exposed to an environmental factor (but not genetically susceptible), or all gene
carriers (but not exposed to the environmental factor).

• Not all exposed to an environmental factor or gene carriers face equal cancer risk.

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 GOALS OF MOLECULAR EPIDEMIOLOGY

• Better estimation of exposure, including ‘internal’ exposure, through the measurement of end-
points (chemical metabolities and adducts)

Eg: Haemoglobin adducts for acrylamide, DNA adducts for PAHs

• Genetic Susceptibility

-Between exposure and effect there is layer of metabolic reaction including activation
deactivation and DNA repair which affects dose-response relationship

• Reduce disease burden by identification of risk factors

-Eg: Association between Aromatic Amines and Bladder cancer

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 WHY MOLECULAR EPIDEMIOLOGY?

• Increase interest of public health workers, physicians, the press and the public at large on
‘environmental risk’ of disease?
• Traditional epidemiology established casual relationships between:
- tobacco smoking and lung cancer
-chronic hepatitis B virus infection and liver cancer
- Aromatic Amines and bladder cancer
• But not all issues of causality in human disease from environmental exposure are so clear.
• But not in case among these two example:
- casual association between dietary exposure to acrylamide and cancer in humans?
- Polycyclic Aromatic hydrocarbons (PAHs) and lung cancer?
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 HISTORY

• The phrase "Molecular epidemiology” for the first time was introduced by
Kilbeurne in 1973 in the article “Molecular Epidemiology of Influenza" .
• The word became more formalized with the preparation of the first book on
Molecular Epidemiology: "principles and practice" by Schulte and Perera. This
book is about impact of advances in Molecular research that have given use age of
its and enable the measurement and explanation of biomarkers as vital tools to
connect traditional and epidemiological research strategic, and also to understand
fundamental molecular mechanisms of disease in the population.
• Science kilbourne's application of the term, "Molecular Epidemiology", has led to
steady growth in the use of the word in about 17000 papers have been published till
now. However this numbers would not ordinarily deemed by a large number, nor
this include the vast explosion of scientific literature on biomarkers, genetics 7
enzymology as well as molecular and cell signaling of disease, all of which lend
 WHY MOLECULAR EPIDEMIOLOGY?

• For this reason started at least in 1982 with a paper by Perera and Weinstein but
probably before with a paper by Lower (Vineis 2007),’molecular epidemiology’ was
introduced into ‘cancer research’ .
• This corresponds to one of the first definition of molecular epidemiology.

“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 and Weinstein 1982

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 ME- CONCEPT

• Molecular epidemiology refers to the use of molecular biology techniques in epidemiologic research.

• Molecular epidemiology emphasizes the role of each genetics and environmental factors that
influence disease process at molecular levels.

• The term was first popularized in the context of infectious diseases, and in the early 1980s it was
applied to chronic disease research.

• Schulte defined the term as “the incorporation of molecular, cellular, and other biologic
measurements into epidemiologic research”.

• With the introduction of genomics, proteomics and meta-bonomics ME started growing

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 ME- CONCEPT

• Molecular epidemiology can be defined as the application of the techniques of molecular

biology to the study of the epidemiology of disease in human populations. Molecular
investigations, as we will see, have several aims and can contribute to the elucidation of
disease etiology.

• In molecular epidemiology, the study of the determinants of disease focuses on causative,

protective, or predisposing factors (including infectious agents and a variety of
environmental exposures such as chemical or physical agents and lifestyle habits) and
host characteristics such as genetic susceptibility. These studies are performed at the
molecular level using the techniques of molecular biology.

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TRADITIONAL VS MOLECULAR
EPIDEMIOLOGY?
Chromosome aberrations
Gene Mutations
Gene Expressions and
Epigenetics

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 TRADITIONAL VS MOLECULAR
EPIDEMIOLOGY?
• Traditional epidemiology is concerned with correlating exposures with outcome, and
everything between the cause (exposure) and the outcome is treated as a “black box.”

Traditional Epidemiology Molecular Epidemiology

Studies are performed using:
• Databases, mailed questionnaires, or
telephone interviews,
Providing little opportunity for obtaining
the biologic samples necessary for
molecular analyses.
Employ tools for the measurement of
• Exposure,
• Susceptibility
• And disease
( eg: questionnaire, job-exposure matrices,
data from environmental monitoring,
routinely collected health data and
biomarkers)

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 SHIFT FROM INFECTIOUS TO
MOLECULAR EPIDEMIOLOGY

• It gained popularity initially in infectious disease research and later in chronic

disease studies.

• In the field of infectious disease, ME studies have provided valuable information

about infectious disease causation, pathogenesis, circulation, transmission,
prevention, and therapy (Around 2004)

• Molecular epidemiology is primarily applied in cancer research when it comes to

chronic diseases.

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 MOLECULAR EPIDEMIOLOGY
VS
GENETIC EPIDEMIOLOGY

• Molecular and genetic epidemiology represent two separate branches of epidemiology

whose boundaries are overlapping.

• Genetic Epidemiology: Inherited, Clustered in family; identify the unknown genes

that influence risk of malignancies

• Molecular Epidemiology: Finding Biomarkers to link exposure to event, Individual

response, Evaluates the association of variations in
known genes

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 STUDY DESIGN IN MOLECULAR
EPIDEMIOLOGY

• Cohort study

• Case control study

• Nested case-control study

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 USES OF ME

The use of molecular epidemiology methods is meant to provide a specific set of new
tools to answer specific scientific answers:

• A better characterization of exposures, particularly when levels of exposure are

very low or different sources of exposure should be integrated a single measure

• The study of single gene-environment interactions

• The use of markers of early response, in order to overcome the main limitations of
cancer epidemiology
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 USES OF ME

elucidation of disease etiology, distribution pattern and penetrance in families

and population

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 CANCER EPIDEMIOLOGY?

Environment
Metabolic activation Cancer
(Phase I enzymes
eg:P450s)

Carcinogen
Metabolic detoxification Replication (cell-cycle
(Phase II enzymes eg: GST, control eg: H-ras1, p53,
NAT, UGT) p21)
Reactive
DNA Genetic
intermediates
adducts damage
DNA repair
Excretion eg: XRCC1 Normal DNA Cell death 18
 MOLECULAR EPIDEMIOLOGY TOOLS

1. Conventional Methods
• Culture
• Enzyme-linked immunosorbent assay (ELISA)
• Enzyme immunosorbent assay (EIA)
• Antibodies & Monoclonal antibodies based assays, agglutination etc.

2. Nucleic acid based Methods

• DNA hybridization for known genes
• Direct sequencing of one or more regions
• Multilocus sequence typing (MLST)
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 MOLECULAR EPIDEMIOLOGY TOOLS

3. PCR (nucleic acid amplification) based Methods:

• Amplification of a single target specific to a pathogen

• Ligase chain reaction (LCR)

• Loop mediated isothermal amplification (LAMP)

4. Protein based Methods:

• Western blot or Immunoblotting.

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 REFERENCES

1.Molecular epidemiology of chronic disease. Chris wild, Paolo Vineis, Seymour

Garte. 2008
2.https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/canjclin.55.1.45
3.Molecular epidemiology of cancer
4.Toward an Integrated Approach to Molecular Epidemiology. American
Journal of Epidemiology, Volume 146, Issue 11, 1 December 1997, Pages 912–
918
5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880254/pdf/f1000research-8-
21700.pdf

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