Introduction of Cancer Molecular Epidemiology 243 ZuoFeng Zhang

Introduction of Cancer Molecular Epidemiology 243 Zuo-Feng Zhang, MD, Ph. D University of California Los Angeles

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

Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. NEJM, 2000

Definition of 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

Epidemiology and Molecular Sciences Epidemiology • Health effects in grouped people • Observation and inference of association between variables • Macro Molecular Sciences • Assessment of the individual at the component level • Experimental proof of cause and effects • Micro

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

Revolution in Molecular Biology: • Science • Medicine • Human Genetics • Public Health • Epidemiology • Chemistry Molecular Epidemiology

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.

Traditional and Molecular Epidemiology Traditional • Association • High exposure and single outcome • Prevention through control of exposure is feasible without understanding cellular process Molecular • Mechanisms • Smaller and mixed exposures; multicausal • Intervention through cellular process has the need to understand mechanisms of the process

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

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

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.

Biological Markers Measurement of Biomarkers can be measured quantitatively or qualitatively by biochemical, immunochemical, cytogentic, molecular and genetic techniques.

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.

Biological Markers: The 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.

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

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

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

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

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.

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.

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.