At a Glance

Focus: Students analyze a Web-based case study about a family's decisions related to testing for particular genetic variations that increase susceptibility to breast cancer and consider how understanding the related science can help people make decisions in uncertain circumstances.

Major Concepts: Our growing understanding of human genetic variation will allow us to identify genes that are associated with common diseases such as cancer. Genetic testing to identify individuals who have variations that make them susceptible to certain diseases can help people make decisions in uncertain circumstances and holds the prospect for more effective prevention and treatment. However, this capability also raises difficult questions that illustrate the personal and social implications of biological research.

Objectives: After completing this activity, students will

• recognize that our understanding of science can help us analyze and make decisions in uncertain circumstances;
• understand that the ability to identify susceptible individuals through genetic screening and testing holds the prospect for more effective prevention and treatment;
• understand that our ability to identify individuals susceptible to particular diseases also raises difficult questions about the uses of genetic information;
• be able to explain that although it is possible to analyze these questions rationally and civilly, people still may disagree on the answers; and
• understand that science can tell us what we can and cannot do, but we depend on an analysis of ethics and public policy (informed by a sound understanding of the science) to help determine what we should do.

Prerequisite Knowledge: Students should understand that cancer is characterized by uncontrolled growth of cells. Students should also understand that all cancer is fundamentally genetic because it results from the loss of genetic control of the cell cycle. That does not mean that all cancer is hereditary. The form of breast cancer that this activity addresses is one of the hereditary cancers, but it is responsible for only about 5 percent of all breast cancers. Most breast cancers arise from somatic mutations and thus are not hereditary.

Basic Science-Health Connection: This activity highlights the remarkable progress scientists are making in identifying genes related to multifactorial diseases such as cancer and focuses students' attention on the implications such discoveries have for personal health and decision making.

Introduction

This activity offers students the opportunity to apply their understanding of human genetic variation to a fictional case study involving a potentially painful set of decisions that various members of a family have to make. Teams of students analyze the case of a woman, Beth, who is concerned that she may carry a variant of either the BRCA1 or BRCA2 gene that predisposes people to breast cancer. The case study is presented in five segments during which Beth makes two key decisions: (1) to proceed with being tested for altered forms of these genes and (2) after she develops cancer in one breast, not to have a prophylactic mastectomy of the other breast. Students analyze each segment by discussing a set of questions related to the underlying science and to the ethical and policy dilemmas raised by the decisions.

The activity's fundamental purpose is to help students see that an understanding of science and a clear, systematic analysis of options can help us make decisions in uncertain circumstances. Beth has a family history of breast cancer, a form of cancer that kills more than 40,000 women in the United States each year. Information about the presence of the altered gene could help her and her physician be more alert to the possibilities of her developing cancer.

On the other hand, she already is practicing the guidelines recommended to increase the chance of early detection should cancer develop. Furthermore, as students learn, breast cancer related to the presence of an inherited altered gene accounts for only 5 percent of the new cases of breast cancer diagnosed each year, and even if Beth is shown not to carry the altered gene, a certain risk of breast cancer remains. Thus, the decision whether to be tested is complex and is made more so by uncertainty related to the normal human genetic variation that exists among humans. Our understanding of genetic factors that can predispose individuals to certain cancers, while increasing, is still far from complete. The question about whether Beth should request prophylactic mastectomy of both breasts after she develops cancer in one breast is equally complex.

Materials and Preparation

You will need to prepare the following materials before conducting this activity:

• Master 5.1, Analyzing the Issues (make 1 copy per student)
• Human Genetic Variation Web site (1 per team)

Note to teachers: If you do not have enough computers equipped with Internet access to conduct this activity, you can use the print-based alternative. To view and print the instructions and masters for this alternate activity, visit the Masters section.

Procedure

Tip from the field test. Teachers who tested this activity raised two cautions.

• Students became so engaged in Beth's story that they lost sight of the major messages about genetic variation and its relationship to complex disease. Remind your students that Beth's difficult decisions arise because of progress in basic science that allows us to detect such genetic variations.
• Students tended to confuse the test for mutations in the BRCA1 and BRCA2 genes with a test for cancer itself. Be sure to clarify this distinction. The genetic test identifies forms of the BRCA1 and BRCA2 genes that can increase one's likelihood of developing cancer. It is not a test for cancer.

1. Open the activity by asking students whether they know anyone who has had breast cancer. Invite those students who wish to briefly describe their relationship to the individual involved to do so.

With approximately one in eight American women developing breast cancer in their lifetimes, it would not be unusual for one or more of your students to be involved personally with this type of cancer. It may be that the student's mother or another family member has had or currently has cancer. For some of those students, discussions of cancer may be disturbing. We suggest that you watch your students for signs of discomfort (for example, tearfulness, reluctance to begin the activity and unusual silence or reticence) and provide appropriate support.

2. Direct students to organize into their teams and watch the Web-based videos Making Decisions in the Face of Uncertainty (the total running time is about 10 minutes). This first time through, ask students simply to watch and listen so they can get a sense of the complete case.

3. Distribute one copy of Master 5.1, Analyzing the Issues, to each student and explain that now the class will view the videos again, one segment at a time. Suggest that students take notes and list questions that occur to them as they watch each segment, then respond to the related questions on Analyzing the Issues. Discuss each segment in turn, as students complete it, using the questions on Analyzing the Issues as a guide. Address any other questions the students raise, as well.

If students raise questions about the science or legal/policy issues that you and they cannot answer with the materials provided, suggest that someone pursue those answers outside of class.

Segment 1: Considering the Test

Question 1 What decision does Beth have to make?

Beth has to decide whether to have the test for mutations in her BRCA1 and BRCA2 genes. Your students might be interested in the financial aspects of the test. As of mid-1999, when this module was written, the laboratory cost for the combined test for BRCA1 and BRCA2 was about $2,500. The cost for the associated genetic counseling was about $250 to $300. Insurance coverage varies depending on the carrier.

Question 2 Who might be affected by Beth's decision?

Beth, her husband, her mother, her sisters, her teenage daughter, and her daughter's future husband (if she marries).

The identification of mutations that predispose individuals carrying them to cancer is an excellent example of how basic research in science yields results that benefit society. As students complete the activity, challenge them to think about the benefits that Beth and her family gain as a result of this knowledge. Ask students to summarize their ideas as you close the activity in Step 4.

Question 3 What arguments support having the test?

This is a good opportunity to make certain that the students understand the underlying science in this case study. Files in the Reference Database on the Web will help students learn about the science. Students can access those files on their own, if you have enough Web site players, or you can print the materials and distribute them.

Beth will no longer be uncertain about her status with respect to BRCA1 and BRCA2 . She will be able to make some other decisions, and she will be able to inform other family members about whether they are at risk for carrying a mutated form of one of the genes. Note that Beth says, with respect to a potentially negative genetic test, "You find out that you're safe." Ask students to comment on this remark. Emphasize that this test identifies only one type of risk factor for breast cancer. Simply because one does not have the particular mutations identified in this test does not mean that one "is safe" from developing breast cancer. There likely are other unknown genetic variations that can increase one's risk. Furthermore, only a small proportion of breast cancer is hereditary. Beth's comment about birth control pills provides an opportunity to discuss the constantly changing nature of scientific knowledge and to point out the environmental contributions to cancer.

Question 4 What arguments support not having the test?

Beth may not want to know. She will also not have to worry about whether she should share potentially positive test results with other members of the family. She will not have to make tough decisions about detection and/or prevention options (for example, prophylactic mastectomy), none of which is 100 percent effective.

Question 5 What factors do you think Beth and Charlie should consider in making their decisions?

Answers will vary, but be alert for misconceptions about the underlying science.

Segment 2: A Family Question

Question 1 What new facts have you learned about breast cancer?

In testing for genes related to cancer, it is helpful to test a family member who already has had the disease. Not all cancers are heredity. The form of cancer that Beth's mother has may not be heredity. If it is hereditary, it may be associated with a gene not yet identified by scientists.

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