Genes and Medicine

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Revision as of 22:35, 15 April 2010

Genes and Medicine: Family History, Inheritance, and Breast Cancer

Cancer is a genetic disease. It is a disease that results from the accumulation of mutations that leads to uncontrollable cell growth. However, only about 10% of all cancers are inherited. This lesson asks students to apply their understanding of classical genetics to familial breast cancer, breast cancer that begins with the inheritance of a mutated gene. Through the investigation students will develop an understanding of the strategy that was used to identify the genes responsible for this form of breast cancer and of the nature of the genes themselves. After exploring the molecular biology of the disease, students will examine the role of genetic testing in the diagnosis of this form of breast cancer and evaluate the ethics associated with this diagnostic tool.

Lesson Overview

Description of Activity Students begin the activity by evaluating the pedigrees of a small portion of two families in which many of the women have been diagnosed with breast cancer. Applying their understanding of inheritance patterns, the students are asked to consider whether the incidence of the breast cancer in these families is just chance or follows a predictable pattern. With their conclusions in place the students move on to review the methodology used by Mary-Claire King and her colleagues to discover the genetic link to a certain form of breast cancer. The students will read an article explaining the relationship between family history and breast cancer risk, answering questions to ensure their understanding of the relevant biology is in place. From here students move on to examine the nature of the two genes identified as playing key roles in the inheritance of breast cancer. Finally, they examine the power of genetic testing and consider the ethics associated with this diagnostic tool.

Goals and Objectives

Students will be able to:

• construct and interpret a family pedigree.

• evaluate a family pedigree to determine the pattern of inheritance for a specific genetic disorder.

• distinguish between familial and sporadic breast cancer.

• understand the nature of the BRCA 1 and BRCA 2 genes and the role they play in the incidence of familial breast cancer.

• recognize and evaluate the methodology involved in a large scale scientific study.

Common Misconceptions

Students often think: • that the presence of many afflicted individuals in a family indicates the trait being followed is dominant.

• that most incidences of cancer are the result of inheritance.

• that they are too young to develop cancer.

• that if a mutated gene has been inherited it is a guarantee that cancer will develop.

• that only women can develop breast cancer.

The Lesson

Preparation Before class: The lesson handout can be accessed here: Media:Genes_and_Medicine.doc.

Describe any pre-class preparation necessary for the lesson.

Begin the lesson by ensuring that the student’s understanding of the fundamental principles of genetics is in place. This is done by completing the first activity in Part A of the lesson. Have students listen to the interview with Denise (either individually, in small groups, or as an entire class), then present the pedigree provided as a summary of the information she has provided. It is important to note that Denise has provided only a small bit of information about her family, so the pedigree is not very complete. But, there is enough information for the students to deduce an inheritance pattern, although not the right one (as they will find out as they move through the exercise). Also, be aware that are two individuals on the pedigree who are not mentioned by Denise, her sister Vicky and another sister not afflicted with breast cancer. These sisters are included because they will come up again later in the lesson. The first section in Part A has students evaluate a pedigree presented to them, in Section 2 they will construct their own pedigree from a family medical history that has been provided. Once constructed, the students will evaluate their diagrams in an attempt to deduce the inheritance pattern for breast cancer in this family. A discussion of the accompanying questions can focus on both the genetics of the family, as well as the advantages this pedigree might have over the first one presented. Once students realize that adequate determination of the inheritance pattern for a particular genetic disease is dependent upon having a significant amount of data, in other words, an extensive family history, they can listen to the interview with Mary-Claire King linked to the document. This will give them insight into the process that must occur in order to make these sorts of determinations. It will also emphasize the genetic link to breast cancer that Dr. King discovered. The article “Family History, Inheritance, and Breast Cancer Risk,” found in Part B, Section 1, is best read at home. The students should bring in the answers to the accompanying questions for discussion at the next class meeting. It is important to review these answers to ensure that the necessary background on breast cancer is in place. Part B, Section 2 has the students investigating the biology of breast cancer, focusing on the nature of the mutations that give rise to the familial form of the disease. The slides and interviews found at Inside Cancer will provide students with details on the molecular biology of disease. As they work through the slides, they should answer the accompanying questions. In addition to developing an understanding of the nature of the types of mutations that lead to cancer, this part of the web site also gives students the opportunity to see how the “scientific process” is executed in the context of a real problem. It is recommended that students be engaged in a discussion of the methodologies employed, the successes experienced, and the “competition” aspect of science today. The last section of the activity concerns the impact of genetic testing. Here the students listen to the interview with Dr. Barbara Weber. The beginning of the interview may confuse the students as it starts midstream, with Dr. Weber discussing a family with whom she has been working. The key person highlighted in the interview is Vicky. Vicky has been diagnosed with breast cancer and Dr. Weber is analyzing her family history to determine the risk for other members of Vicky’s family. As the interview proceeds Dr. Weber discusses a sister of Vicky’s who has not been diagnosed, but who is considering a preventative bilateral mastectomy. This woman is Denise, the subject of the interview at the beginning of the lesson. This brings the lesson “full-circle” and allows students to see the impact of genetic testing on individuals, as well as families.

The critical point of Part C concerns the ethical aspects of genetic testing.  Students are asked to consider whether or not they would want access to personal genetic information.  They are directed to some reading from The Mayo Clinic to help them see the scope of this issue and then asked to address the issue for themselves, in writing.  After completing the questions in Section 2 of Part C, an in class discussion, or even a debate, can serve as a wrap-up for the lesson.

Describe the activity. Time required

Time allotment for this lesson is dependent upon the extent to which at-home time is used to complete various sections. Below is a list of those components of the lesson that can effectively be completed by the students at home and those best suited for in-class work.

At-Home Work

• Part A: Family Pedigrees: Section 2, Breast Cancer Study – constructing the pedigree and answering the accompanying questions (40 minutes)

• Part B: Identifying the Gene: Section 1: Family History, Inheritance, and Breast Cancer – Read the article and answer the accompanying questions ( 45 minutes)

• Part C: Genetic Testing: Section 2: Complete the assignment at home, bringing ideas into class for discussion (45 minutes).

In-Class Work

• Part A: Family Pedigrees: Section 1 – listen to the interview with Denise, evaluate the family pedigree presented, and answer the accompanying questions (15-20 minutes)

• Part A: Family Pedigrees: Section 3 – listen to the interview with Mary-Claire King about how she used a pedigree for the history of breast cancer in an extended family to determine the genetic link to the disease. A discussion of the methodology she used to make this determination can then take place. Students can compare and contrast the activity they did to the scope of the evaluation needed to determine the genetic link to breast cancer. (15 minutes)

• Part B: Identifying the Gene: Section 2 – work through the Inside Cancer web site as instructed, answering the questions that accompany the slides (30 minutes)

• Part C: Genetic Testing: Section 1 – listen to interviews on slides 1 – 9 and then answer the accompanying questions. Once completed a debriefing on the value of genetic testing can be done. Students can begin to think about and discuss the value of having these sorts of diagnostic tests available, as well as the ramifications of having access to the information that results from these sorts of tests. (40 minutes)

Student Handouts for the Lesson Plan

Photocopy student worksheets: [[Media: Genes_and_Medicine.doc ]] document can be printed out for students prior to class and handed out for them to work on. However, because the links to the necessary online sites are embedded in the text, it may be easier to have students access the document electronically so navigation to the required sites is made easier.

Alternative Assessments

• Teachers may choose to collect and evaluate the answers generated by students to questions asked throughout the activity.

• A short quiz on the information found in the article and at Inside Cancer could be used to assess student understanding of biology of familial breast cancer.

• A formal debate could be organized to present and consider the issues related to genetic testing.

Suggestions for Extended Learning

• While familial breast cancer afflicts 25% of women diagnosed with breast cancer, the remaining 75% of women are diagnosed with sporadic breast cancer. Students could move on from this lesson to investigate the causes associated with this more common form of breast cancer.

Glossary

• Breast Cancer Families - families in which breast cancer is inherited and family members are at greater than average risk of breast cancer.

• BRCA1 and BRCA 2 – Tumor suppressor genes that when mutated are the genes that cause familial breast cancer. • Familial Breast Cancer – A form of breast cancer that is inherited. The mutation in the genome is present before birth, passed down through the germ line.

• Genotype – Identification of the actual alleles present.

• Oncogene - A mutated gene that promotes uncontrollable cell growth. Prior to mutation the gene (known as a proto-oncogene) serves to ensure that cell reproduction only occurs in the presence of appropriate signals.

• Pedigree – A diagram depicting a family’s history with respect to a particular genetic disease that allows the inheritance pattern of the disease to be determined.

• Penetrance – describes the likelihood that a woman who inherits a mutated gene will develop breast cancer. “High” penetrance means a high chance that breast cancer will develop and that there is a high incidence of the disease in the family. “Low” penetrance is characterized by the few occurrences of the disease in a family where the mutated gene has been inherited.

• Sporadic Breast Cancer – A form of breast cancer that results from mutation sustained after birth.

• Stability Gene – Gene that function to control the rate of mutation in other genes in the genome. A mutation in a stability gene leads to enhanced an increased mutation rate in other genes.

• Phenotype – the physical appearance of an individual as a result of the combination of alleles present.

• Tumor Suppressor Gene – A gene whose protein product serves to regulate cell growth by detecting damage to DNA. When mutated, the protein is no longer functional and the cell is allowed to reproduce with damage in place.

Education Standards

• Understanding Scientific Inquiry

➢ Identifying questions and concepts that guide scientific investigations

➢ Formulating and revising scientific explanations and models using logic and evidence

➢ Communicate and defend a scientific argument

• Developing an understanding of Heredity

➢ Heredity information is carried on genes.

➢ The characteristics of an organism can be described in terms of a combination of traits.

• Developing an understanding of the cell and molecular basis of heredity

➢ Genetic information is carried in DNA molecules.

➢ Changes in DNA occur that result in changes to cell structure and function.

• Science as a human endeavor

➢ Individuals and teams have contributed and will continue to contribute to the scientific enterprise.

Teacher Answer Key

Answer key can be accessed here: Media:Genes_and_Medicine_+_answers.doc