Epidemiology and Genetic Susceptibility

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 MARIANA C. STERN 

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089 

Molecular and Biochemical Toxicology, Fourth Edition, edited by Robert C. Smart and Ernest Hodgson Copyright 2008 John Wiley Sons, Inc. 

In the present chapter we will first review basic concepts of epidemiological research and follow with a discussion of different types of biomarkers used in molecular epidemiology, and finally we will concentrate on the study of genetic susceptibility. In our discussion we will put special emphasis in the challenges that using such markers introduce when used at the population level. 

The obj ective of epidemiological studies is to determine whether a causal relationship exists between a putative risk or protective factor and disease. Thus, most studies are designed to test a hypothesis Does exposure (e.g., consumption of cooked meats) cause disease (e.g., colon cancer) After the study is conducted, the data are analyzed and the magnitude of the putative association between exposure and disease is calculated. The study is then evaluated to see whether the association (if observed) could be a result of random or systematic errors or whether other exposures or factors are influencing the exposure of interest (i.e., effect modifiers). 

---

Besides age, the development of colorectal cancer appears to be caused by variety of dietary or environmental factors, comor-bid disease states, and genetic susceptibility to the disease. Table 88-1 lists well-known risk factors for developing colon cancer. Epidemiologic studies of worldwide incidence of colorectal... 

Asthma rates in children in Southern California are high and oxidant pollution levels are likewise high. It is important to determine the relationship between the two. It is also important to determine whether there are chronic pulmonary effects produced by either these oxidants and/or particulate pollution. Since children spend more time outdoors than adults and since they exercise more while outdoors, the added assault from increased ventilation may be of importance. The studies feature a comprehensive exposure assessment that has led to a better understanding of the relationship between exposure and effects. It is also important to identify sub-populations of children and adults who are more susceptible to air pollution-related respiratory effects if they exist. Altered susceptibility could be based on genetic or non-genetic mechanisms (nutritional status for example). Both the epidemiologic and chamber studies provide opportunities to examine issues of hypersusceptibility and to determine the reasons for it if it exists. 

The challenge for molecular epidemiological studies on genetic susceptibility consists of identifying which of these genetic variants can contribute to disease risk and also identifying which ones can modify the effect of environmental exposures. Until now, the approach that most studies have taken to answer these questions has... 

Sturgis EM, Wei Q. Genetic susceptibility-molecrrlar epidemiology of head and neck cancer. Curr Opin Oncol. 2002 14(3) 310-317. 

---