Christopher I Amos Carol H Bosken Amr S Soliman and Marsha L Frazier

Chapter Overview 67

Introduction 68

Identifying Epidemiologic and Genetic Risk Factors for

Colorectal Cancer 69

Cohort Studies 70

Assessing Familiality and Segregation Analysis 70

Factors Associated with Risk for Colorectal Cancer 71

Inflammatory Bowel Disease 71

Factors Related to a Western Lifestyle 72

Calcium and Folate Supplementation 73

Cigarette Smoking 73

Nonsteroidal Anti-inflammatory Drugs 73

Hormone Replacement Therapy 74

Screening 74

Genetic Factors 74

Hypermethylation and Colorectal Cancer 78

Gene-Gene Interactions 78

Environmental Factors Related to Hereditary and Familial

Colorectal Cancer 79

Conclusions 80

Key Practice Points 81

Suggested Readings 81

Chapter Overview

A wide range of environmental factors influence risks for colorectal cancer. Patterns of food consumption, exercise, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) affect risk for colorectal cancer. The strong risk reduction for colorectal cancer associated with NSAID use provides a strong rationale for chemoprevention studies. However, in considering the application of any chemopreventive agent, the risk and impact of side effects must be considered. Other possible interventions, such as behavioral modification to increase exercise, would most likely reduce the risk for colorectal cancer, but effecting this type of change may be difficult.

Genetic studies can provide novel insights into the etiology of colorec-tal cancer. Case-control studies may be readily conducted and have provided novel insights into the role of DNA repair and metabolic genes in colorectal cancer causation. Cohort studies may avoid some biases associated with selection into case-control studies but are often complex and costly to conduct. In this chapter, we describe and compare these approaches.

At M. D. Anderson Cancer Center, we have focused primarily on the study of individuals at genetically high risk for colorectal cancer. Subjects at high risk for cancer are most likely to benefit from chemopreventive strategies and can provide the greatest information about novel screening modalities. However, findings from high-risk subjects may not generalize to a broader population, and large studies are needed to evaluate the role of genetic and environmental factors in lower-risk populations.

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