Introduction of Cancer Molecular Epidemiology

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Introduction of Cancer Molecular Epidemiology

• Epidemiology 243
• Zuo-Feng Zhang, MD, PhD
• University of California Los Angeles

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Numbers of Papers with Subject Words Molecular
Epidemiology on Medline
80-84
05-09
70-79
90-94
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Definition of Epidemiology

• Epidemiology
• Describe distribution patterns of the disease
  among population, time trend, and places
• Identify determinants (risk factors/etiological
  factors) of the disease
• Disease prevention and control conduct
  intervention studies to reduce incidence and
  mortality of the disease

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Epidemiology and Molecular SciencesEpidemiology
Molecular Sciences

• Health effects in grouped people
• Observation and inference of association between
  variables
• Macro

• Assessment of the individual at the component
  level
• Experimental proof of cause and effects
• Micro

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Evolution of General Epidemiology

• Advances in molecular biology, genetics,
  analytical chemistry, and other basic sciences
  have made it possible to measure contaminants,
  carcinogens, biological changes at a much smaller
  level.
• These advances can assist us to assay genetic
  susceptibility by genotyping and other genetic
  methods and to identify mechanisms at cellular
  and molecular levels

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Revolution in Molecular Biology

• Science
• Medicine
• Human Genetics

• Public Health
• Epidemiology
• Chemistry

Molecular Epidemiology
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Molecular Epidemiology

• The goal of molecular epidemiology is to
  supplement and integrate, not to replace,
  existing methods
• Molecular epidemiology can be utilized to enhance
  capacity of epidemiology to understand disease in
  terms of the interaction of the environment and
  heredity.

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Traditional and Molecular EpidemiologyTraditiona
l Molecular

• Association
• High exposure and single outcome
• Prevention through control of exposure is
  feasible without understanding cellular process

• Mechanisms
• Smaller and mixed exposures multicausal
• Intervention through cellular process has the
  need to understand mechanisms of the process

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Molecular Epidemiology

• studies utilizing biological markers of exposure,
  disease and susceptibility
• studies which apply current and future
  generations of biomarkers in epidemiologic
  research.

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Basics of Molecular Epidemiology

• The term of molecular epidemiology indicates the
  incorporation of molecular, cellular, and other
  biological measurements into epidemiologic
  studies

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Biological Markers Definition of Biological
Markers

• Biological markers can be currently defined as a
  biological product related to any sequence of
  multistage carcinogenesis, including tumor
  initiation and promotion.

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Biological Markers Measurement of Biomarkers

• Biomarkers can be measured quantitatively or
  qualitatively by biochemical, immunochemical,
  cytogentic, molecular and genetic techniques.

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Biological Markers Materials for Biomarker
Measurement

• Biomarkers can be measured in human biological
  materials including normal and tumor tissues,
  blood and urine sample, etc.. Their biological
  nature can be DNA, RNA, and protein, etc.

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Biological MarkersThe Application of Biomarkers

• Biomarkers can be employed to predict primary or
  secondary cancer risk, to establish cancer
  burden, to further classify the tumor in addition
  to pathological classification, to predict tumor
  prognosis, to determine treatment strategy, and
  to evaluate chemo-prevention or intervention.

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Capacities of Molecular Epidemiology

• Identification of Exposure at the smaller scale
• Identification of events earlier in the nature
  history of disease
• Assay susceptibility markers and evaluation of
  gene-environment interaction
• In addition, it can be used to reduce
  misclassification, to indicate mechanisms, and
  enhance risk assessment

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Molecular Epidemiology

• These capacities provide additional tool for
  epidemiologists studying questions on etiology,
  prevention and control of diseases
• Although molecular epidemiology can be viewed as
  an evolution step of epidemiology, it generally
  dose not represent a shift in the basic paradigm
  of epidemiology

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Study of Black Box

• The concept of a continuum of events between
  exposure and disease provide opportunities
• To ensure that epidemiologic research has a
  biological basis for hypothesis
• To provide the analysis to test these ideas
• To generate new epidemiological methods to deal
  with new challenges

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Application Risk Assessment

• Molecular epidemiology focuses on identifying
  high risk individuals and make personalized risk
  assessments by measuring changes at molecular
  level, particularly those entailing structure
  gene damage, gene variation, or the measurement
  of gene products in cells and body fluids

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Application Genetic Predisposition or
Susceptibility

• Molecular epidemiology utilizes a series of
  biological markers (exposure, susceptibility,
  early biological response markers), which include
  genetic predisposition and susceptibility markers
  which are usually the major focus of the genetic
  epidemiology.

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The application of Biomarkers

• Biomarkers can be employed in primary preventive
  or etiological research by detecting the
  relationship between environmental exposure and
  specific mutations.
• These can be utilized in secondary preventive
  studies or early detection and diagnosis by
  identifying markers for tumors at early stage or
  precursor of tumor.
• Finally, these markers can be used in tertiary
  preventive studies or prediction of prognosis by
  correlating biomarkers with tumor progression and
  patient survival.

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Tasks for Molecular Epidemiologist

• The major tasks are
• to reduce misclassification of exposure,
• to assess effect of exposure on the target
  tissue,
• to measure susceptibility/inherited
  predisposition to cancer,
• to establish the link between environmental
  exposures and gene mutations,
• to assess gene-environment interaction.
• To set up prevention/intervention strategies.