Victor R. Grann, MD, MPH
Clinical Professor of Medicine and Epidemiology

Judith S. Jacobson, DrPH, MBA
Assistant Professor of Epidemiology
Columbia University College of Physicians and Surgeons
New York, New York

Screening is the use of a medical test in a well-defined group of individuals with no symptoms of a specific disease (such as breast or cervical cancer) in order to identify those who have either undetected disease or an elevated risk of developing that disease. New screening tools that focus on genetic changes, or mutations, are receiving more and more attention. Over the past five years, a number of these tests for inheritable gene mutations associated with a high risk for diseases such as breast cancer have become available (Table 1). These tests, when used properly, may lead to reductions in both disease complications and death.

Common cancer screening tests, such as mammography (for breast cancer) and sigmoidoscopy (for colon cancer), differ from tests that look for cancer-related gene mutations in several respects (Table 2). Most cancer screening tests detect but do not predict disease. For that reason, individuals who have had a negative (normal) test result usually need to be tested again on a regular schedule because a later test may well be positive. The recommended interval between tests depends mainly on what is known about how the disease develops.

Cancer screening tests provide information only about the individual tested; they identify conditions that occur often enough, or are serious enough, to justify testing all asymptomatic individuals in a defined group of people (e.g., every adult over age 50 years for colorectal cancer). These tests involve sampling or imaging the target tissue or organ. Some cancer screening tests, such as colonoscopy and Pap smears, can lead to the identification and removal of precancerous lesions, thereby reducing the patient's risk of developing invasive cancer. But more often, these and other screening tests, such as mammography, do not prevent the development of the disease; they serve only to identify the disease at an earlier stage, when treatment is more likely to prevent death.

In contrast, genetic tests can identify cancer-related inheritable mutations in cells from any easily sampled tissue (e.g., blood) in disease-free individuals or in patients with the disease who have unaffected family members who may be at risk and can also be tested. Disease-free individuals who test positive for cancer-related mutations are candidates for aggressive primary preventive measures. To the extent that such measures are available and effective, genetic testing can prevent people at high risk for cancer from developing the disease. In addition, genetic tests need to be done only once per individual.

However, these tests are not for everyone. Inheritable gene mutations that cause significant morbidity and mortality at a relatively young age are generally quite rare in the population for obvious evolutionary reasons. Tests for cancer-related inheritable mutations should therefore not be used in the general population. Candidates for genetic testing should meet specific guidelines that usually involve either family or personal medical history or membership in a specific ethnic group in which the mutation is known to be common.

Ideally, randomized clinical trials or observational studies should be in progress now to assess the costs, quality of life, and survival associated with genetic testing as well as the use of preventive strategies by those individuals who tested positive. Although a few observational studies are in progress, their results are not yet available. Meanwhile, patients, physicians, and policy makers still need to make decisions about testing.

Familial cancer risk is a sensitive issue. In our preference rating survey, individuals who were thinking about undergoing genetic testing were less concerned about their personal risk for cancer than about the possible increased risk of their children. An individual who tests positive for a cancer-related inheritable mutation has a moral obligation to notify at-risk relatives, but it is not pleasant to have to tell one's relatives that they may be at risk for a serious disease because of an inheritable gene mutation. Family members often differ in their willingness to find out whether they have the mutation or to share that information with others. Genetic counseling can help individuals and families to deal with these issues and may be essential to the success of a genetic screening program.

The future holds the promise of rapid, inexpensive, and accurate tests that may empower individuals to make preventive treatment decisions that enhance their lives. However, even if genetic tests become very inexpensive, they will not be appropriate for general population screening because of the evolutionary-based rarity of these mutations. If genetic screening policy is based on sound epidemiological principles, rather than on consumer demand and third-party willingness to pay, it holds the potential to enhance the public health and the public good.