1. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 1 Native Cancer 101 Module 4: Role of Genes in Cancer Intermediate (science students, beginning professionals) version estimated time: 120 minutes with Participant interactivity 02-02-2013 version with ARS Linda Burhansstipanov, MSPH, DrPH Native American Cancer Initiatives, Incorporated (NACI) 3022 South Nova Road Pine, CO 80470-7830 http://www.NatAmCancerInitiatives.org Lynne Bemis, PhD, Head of Biomedical Sciences Department University of Minnesota School of Medicine, Duluth Campus

2. Assumptions This is a workshop that should follow several other topics (e.g., overview of cancer among AI/ANs, importance of cancer screening, etc.). Thus, it is not an introductory topic. This includes scientific and cultural information specific to genetics and cancer. The workshop facilitator / faculty is/are NOT interested to collecting genetic samples from you.

3. Please turn off your cell phones or switch them to “vibrate” mode

4. Audience Response System (the Keypads) (TP)

5. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Turning Point Keypads Lanyard that goes around your neck These are NOT calculators and need to be returned to the faculty at the end of the session please

6. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Audience Response System (ARS) – keypads This is how we vote on different items and issues Although the keypads are “anonymous” (we don’t know who uses which keypad); but we would like you to use the same one throughout the workshop You do not need to “point” the keypad (like a TV remote control) You will see a counter on the screen that shows how many people have “voted” on any item You press the number on the keypad that best describes your answer (use “0” for “10” on the keypad)

7. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Audience Response System (ARS) – keypads You can change your vote up until the final vote has been collected and the slide advances A top bar appears and the upper right-hand box needs to be “green” before you vote. A summary of bar graphs appears on the screen after the votes are completed for most items so that everyone can see the total tallies The summary bar graph will not appear for pre- workshop knowledge items or workshop satisfaction

8. 5 Demographic items (TP)

9. What is your gender? 1.Male 2.Female 3.Don’t want to answer

10. brthyr5 About How Old are You? 1.81 and older 2.65-80 3.50-64 4.41-49 5.31-40 6.21-30 7.13-20 8.Under 12 9.Don’t want to answer

11. What is Your Primary Race? 1.American Indian / Alaska Native (AIAN) 2.Pacific Islander 3.Asian 4.African-American 5.Non-Hispanic white (Caucasian) 6.Other 7.Don’t know / Don’t want to answer

12. Are you Hispanic, Latino or Chicano? 1.Yes 2.No 3.Don’t Know / Not sure 4.Don’t want to answer

13. How Much Schooling have You Completed? 1.Elementary (kindergarten through grade 6 / grade school) 2.7 th, 8 th, or 9 th grade (middle school) 3.10, 11, or 12 th grade (no degree) 4.High school graduate / GED 5.Technical school /apprentice training 6.Some college (no degree) 7.College AA degree 8.College BA, BS degree 9.Masters’ degree 10.Doctorate or more

14. Personal Experience Questions (TP) 2 items

15. How much science education have you completed? 1.None 2.Between 1-6 hours 3.Between 7-14 hours 4.15+ hours 5.Don’t know / Don’t want to answer`

16. Have You ever been Told by a Healthcare Provider that you have Cancer? 1. No 2. Yes 3. Don’t know 4. Don’t want to answer

17. 5 Pre-Session Knowledge Items

18. Which has the biggest / greatest impact on cancer risks for most people? 1.Exposure to radiation 2.Characteristics inherited from your mom and dad 3.Exposure to environmental contaminants 4.Daily lifestyles (diet, exercise, tobacco use) 5.Don’t know / Not sure

19. Which is TRUE about BRCA2? 1.Is a large gene (many base pairs) on the 13 th chromosome 2.Is responsible for ~25% of all breast cancers 3.Has no effective cancer treatments to control or manage the disease 4.Is only found in females 5.Don’t’ know / Not sure

20. Obj 2 – Which chromosome is the largest? 1.22 2.16 3.12 4. 5 5.Don’t know / Not sure

21. Obj 7 - How would you refer to the short arm of chromosome 3? 1.3Cp0 2.3q 3.3mRNA 4.3p 5.Don’t know / Not sure

22. Obj 5 / 19 - What type(s) of community approval are required for a research project to be conducted in an American Indian community? 1.Academic approval 2.Community / tribal institutional review board (IRB) 3.Traditional Indian healer’s blessing 4.Tribal college approval 5.Don’t know

23. Native Cancer 101 Module 4 (Role of Genes) Objectives. By the end of this session the participant will be able to: 1.Define basic genetics terminology 2.Describe the role of genes in cancer and cancer treatment 3.Describe the benefits and limitations of genetics testing 4.Discuss the benefit of recording your family health history – if time 23

24. Introduction and overview 24

25. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Examples of Genetic Traits Tongue rolling Hand clasp Ear lobes Arm folding 25

26. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 26 Genetics is not new information for AIANs Our ancestors knew how to Breed horses (Pintos, Appaloosa) so that their coloring blended with rocks, ground or aspens during the winter Grow stronger, more disease-resistant crops (e.g., corn and squash) ©Bev Doolittle. Used by permission of The Greenwich Workshop, Inc. for inclusion in this slide presentation, handout only

27. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 27 Genetics is not new information for AIANs The concept of genetics is not new, but: How genetics is being used today New words created to describe genetic science today New cultural issues for protecting privacy of individual and tribal Nations today New science that can be generated to help address common health problems (diabetes, cancer) among Natives today... Those are new ideas and concepts for AIANs

28. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; QUESTION: Why is this important for AI/AN communities? Cancer = increased among AI/ANs People may learn their cancer risk, but: Is there an effective cure or treatment? Are there people trained to explain the cancer risk (is the risk real?) New treatments are at the genetic and molecular level and the information may impact patient care. 28

29. Objective 1: Define basic genetics terminology genes, chromosomes, DNA, mutation, heredity 29

30. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 30 What are “genetics”? What are “genes”? “Genetics” is the study of “genes” “Genes” contain the information for the body to function Some genes make bones strong Other genes help prevent cancer (tumor suppressor) A gene is a segment within a chromosome

31. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 31 Chromosomes Organized by researchers from the largest / longest (number 1) to the smallest (number 22). The longer the chromosome, the more genes

32. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 32 Chromosomes (continued) DNA (Deoxyribonucleic Acid) molecules refer to the genetic information that is within the chromosomes Chromosomes are in the “nucleus” (“brains” of the cell) Chromosomes are packed with thousands of genes Genes tell our cells what to be and how to act

33. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 33 “Genes” and “Mutations” The pattern of information within genes needs to follow a specific sequence for the cell to function correctly. When the sequence differs, it is called a “mutation” (or SNP, pronounced “snip”) Everybody has mutations (or SNPs) that may cause: A different effect or function of the gene The gene to continue having the normal function

34. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 34 Example: p53 (“The Big Guy”) Human chromosomes have a segment containing a gene called “p53” Dr. Bemis calls “p53”, “The Big Guy” More than half of all tumors have damage in the area of the gene that makes up “p53” p53 helps protect the body against cancer p53 is a tumor suppressor Unless it is damaged (mutation)

35. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 35 More about “Genes” (continued) The nucleus has genetic information provided from your mother and from your father. The human body has about 20,000 genes. Every human being is 99.9% similar to any other human being That 0.1% of genetic information is why and how we look and are different from one another

36. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 36 QUESTION: What does “heredity” mean? Heredity” means that the characteristic came from the sperm and egg (from your dad and mom) when you were conceived in the womb 23 chromosomes from dad (sperm) and 23 from mom (egg); a copy of each chromosome to fertilized egg

37. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 37 Causes of Cancer Daily Behavior / Lifestyle (not enough physical activity, unhealthy food, excess alcohol, habitual use of tobacco) = cause changes in genes within body cells Environment (exposure to contaminants, e.g., asbestos) = cause changes in genes within body cells Heredity (chromosomes from mother and father that created the fertilized egg that resulted in the child) = only 5-10% of all cancers

38. Objective 2: Describe role of genes in cancer 38

39. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 39 Role of genes in cancer Only a small group of mutations directly associated with cancer risk are inherited from the parents Other (i.e., “most”) mutations are acquired over the life span Multiple injuries occur to the same cell to evolve or result in cancer “Injuries” can be from alcohol abuse, exposure to commercial tobacco, bacteria, virus, inactivity, unhealthy diet

40. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 40 Role of genes: mutations The injury is a mutation resulting in damage that is passed on from the first body (somatic) cell as it divides into additional cells It gives the cells harboring the mutation an advantage to outgrow other cells For example in lung cancer the carcinogens in cigarette smoke may cause damage in several genes

41. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 41 Role of genes: mutations (continued) One change may allow the cells to grow out of control while another may cause the cells to be resistant to therapy Multiple injuries are required before the cells are changed enough to allow them to grow out of control For most solid tumors, 5-10 separate “injuries” occur before the cell becomes cancer

42. Interactivity: Chromosome Ropes Rope chromosomes (100,000 of times larger than actual chromosomes) Telomere Centromere “Single Nucleotide Polymorphism” (SNP) / mutation p seqment q segment Longest chromosome =1; Shortest chromosome = 22 Germ (sex) cells (2) 42

43. Interactivity: Chromosome Ropes Chromosome ropes are in a pile. Please go to the pile and select 1 chromosome. Please look at the chromosome What is the number of your chromosome? Is it longer or shorter than the chromosome of the person sitting next to you? Find others in the room who have a rope the same length as yours. Gather as a group and 1 person comes forward to get the “model” rope chromosome Where is the “centromere”? Do you have a “Single Nucleotide Polymorphism” (SNP)? Where is the SNP located? p? or q? What disease is related to your SNP? 43

44. Interactivity: Chromosome Ropes Where is the “centromere” on the model”? Please tie a knot centromere on your chromosome. Does the model have a “Single Nucleotide Polymorphism” (SNP)? What is it and what does it do? Where is the SNP located on the model? p? or q? Please make your rope look like the model rope chromosome 44

45. Interactivity: Chromosome Ropes Form pairs with someone who has a chromosome that differs from yours Based on the 2 chromosomes in your group, is the person likely to have cancer? Why or why not? Is / Are your SNP(s) contributing or preventing cancer Now find another group (i.e., 4 chromosomes). is the person likely to have cancer? Together, create a new cancer-related SNP What does your made-up SNP do? 45

46. Interactivity: Chromosome Ropes Together (group of 4), create a new cancer- related SNP What does your made-up SNP do? 46

47. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 47 Role of genes in cancer (continued) A variety of genes are known to be ‘injured’ in cancer. Two overall types of injuries occur Those that block the expression of “Tumor suppressor” genes like p53, BRCA1 and BRCA2 Those that activate oncogenes (genetic markers / SNPs that contribute to cancer) KRAS, BRAF, EGFR

48. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 48 Tumor Suppressors Those genes whose normal function is to suppress the overgrowth of cells. For example: p53 is known as the guardian of genome p53 is a guardian because it protects the cell from damages such as radiation or other stress p53 Families and Li-Fraumeni

49. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 49 Tumor Suppressors People who have a disease called Li Fraumeni generally inherit a mutation in p53 and their cancer rate is much higher than the rest of the population It is thought that treating a patient who has a mutation in p53 with radiation increases their risk for additional cancer incidence If a patient has Li-Fraumeni (p53) damage, would they receive radiation?

50. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 50 Oncogenes and Adapted Cancer Treatments Oncogenes are genes that are over- expressed, allowing the growth of the tumor or increases the aggressive nature of a tumor. Mutations in BRAF are a good example in melanoma because it allows for the uncontrolled growth of melanoma cells.

51. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 51 Oncogenes and Adapted Cancer Treatments Mutations must be detected for patient to receive drug targeting BRAF because if given to patients without a BRAF mutation they may become more sick due to the effects of the drug Obviously learning more about these oncogenes can predict more effective cancer treatments with fewer side effects

52. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 52 Researchers Study Molecular Pathways Researchers study “pathways” for how oncogenes reach the cancer tumor cells These are molecular pathways that tell the tumor cell to grow grow grow (also called “amplification”) EGF Binds to Receptor Growth Signal Pathway Epidermal Growth Factor (EGF) EGF Receptor Nucleus Cell growth

53. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 53 Researchers Study Molecular Pathways Researchers try to find other molecules that would block that pathway so that the cell never receives the signal to grow grow grow Pathways

54. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 54 Cancer Treatment: cetaximab Cetaximab is an antibody (protein acceptable to human body) that attacks receptors on cancer cell so that the cancer cell cannot multiply Attacks oncoproteins such as Epidermal Growth Factor Receptor (EGFR) Pathway blocks blinding of EGF and prevents growth signal

55. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 55 cetuximab Epidermal Growth Factor Receptor EGFR is a receptor on the cell’s surface Found on many cancer cells (lung, CRC) The EGFR protein gives improper signals to the tumor cell to grow grow grow EGF Binds to Receptor Growth Signal Pathway Epidermal Growth Factor (EGF) EGF Receptor Nucleus Cell growth

56. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 56 Based on this type of Research If you give the patient cetuximab, the cetuximab goes to the EGFR protein and blocks its ability to send “grow grow grow” signals Patient is tested for KRAS mutation prior to CRC treatment Currently the clinical lab needs a biopsy of the tumor The test for KRAS is a blood test QUESTION: If the patient has the KRAS mutation, should he receive cetuximab? ANSWER: No. the drug doesn’t work on people with this KRAS mutation in their tumor

57. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 57 95% of pancreas cancers have KRAS Mutation This is why cetuximab cannot be used to treat pancreas cancer Likely to need a different drug (e.g., mTOR inhibitors) to target this signal

58. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 58 Chromosomal changes in Cancer There are frequent mutations in cancer cells Sometimes there are large rearrangements Sometimes there are deletions of part of a chromosome Sometimes there are small changes that may only be detected with PCR or other genetic tests. NOTE: PCR stands for polymerase chain reaction. This is the method that allows researchers to copy and amplify almost any piece of DNA to better understand it. Many of the genetic tests currently in use require PCR as part of the process of determining if the patient has a SNP

59. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 59 Chromosomal Changes in Cancer Sometimes a test can be developed that looks at large regions of DNA changes Other times a few regions of a gene are examined BRCA1 and BRCA2 are very large genes known to harbor many mutations that may be passed from the parent to child

60. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 60 QUESTION: What is a BRCA2 mutation? BRCA2 is a protein that helps to repair certain kinds of damage to DNA BRCA2 is a very large gene composed of 84,188 base pairs Hundreds of mutations have been discovered in BRCA2 and some are associated with certain ethnic groups SEE YELLOW LAMINATED SHEETS WITH BRCA2 SUMMARY INFO (or use the following yellow slides end of module)

61. 61 Scenario: Mary Lou (your sister) was just diagnosed with breast cancer Please form groups of 4 and review the yellow laminated BRCA2 summary) BRCA2 is a genetic form called “BRCA2” (BR from “breast” and CA for “cancer” and “2” because it was the 2 nd hereditary breast cancer gene Catherine, your other sister doesn’t know if she is carrying the same type of genetic marker (BRCA2) What additional information do you want before you decide whether to have the BRCA2 test?

62. Objective 3: Describe potential benefits and drawbacks of genetics testing 62

63. 63 Mary Lou Scenario continued The BRCA2 test is expensive ($1200). Who will pay for the test? What are your options? Will IHS pay for BRCA2 testing? Who do you think SHOULD pay for the test? Do you know of any clinical trials in your area that may pay for the BRCA2 test? How would you find such a clinical trial?

64. 64 Scenario continued Catherine (Mary Lou’s sister) decided to have the test and her results were negative. How does that impact or affect your potential test results? Craig is your older brother. He is having problems with an enlarged prostate. Mary Lou told him that BRCA2 is related to prostate cancer in men. Now Craig is fretting.

65. Using BRCA2 As An Example Having the marker (BRCA2) does not mean you will develop cancer The marker indicates a predisposition Every single person has a BRCA2 gene, but only a few have a mutation Populations at risk are on following page 65

66. Using BRCA2 As An Example Populations who may carry the mutation BRCA2 mutation(s) Result of the mutation Ashkenazi Jewish 6174delT A deletion of a T base results in a shorter than normal protein Dutch5579insA An extra base (A) causes altered expression of the protein French Canadians 8765delAG In this case two base pairs are missing 66

67. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 67 Possible Personal Benefits of Genetic Testing QUESTION: What are examples of some ways that an individual may personally benefit from participating in genetic tests? Medical and lifestyle choices are available for selected conditions Learns whether s/he does or does not have an altered gene Learns to cope with the personal risk

68. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 68 Possible Personal Benefits of Genetic Testing Decide whether or not to have surgery (possibly protective surgery) Provide useful information to other family or tribal members Contribute to research If people know that “genetic” risk is not the cause of disorder, more likely to address behavioral / lifestyle “risks” Change behavior (e.g. take part in screening)

69. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 69 Possible Personal Benefits of Genetic Testing More effective and efficient treatments tailored to the individual An example is the relatively new field of science called, “pharmacogenetics” The study of medications and genetics

70. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 70 How Might the Tribe or Other Native Americans Benefit by an Individual Participating in Genetic Testing? Information about common conditions may be helpful to others Communities can focus on behavior changes rather than assume “fatalistic” attitude about a disease

71. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 71 Possible Drawbacks to Genetic Testing A genetic “mutation” that NEVER results in a disease (i.e., worry about “nothing”) What does “lifetime risk” mean? How does “lifetime risk” relate to tribal beliefs or cultural mores? Genetic “mutation” may be present, but there may not be “treatment”

72. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 72 Possible Drawbacks to Genetic Testing The test may be limited to only one part of a gene, and not the part of the gene that has the mutation (the test is “limited”) The test may be inaccurate “false positives” or “false negatives” Negative test results may provide a false sense of security An individual may find it harder to cope with the cancer risk when s/he knows the test results

73. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 73 Possible Drawbacks to Genetic Testing You may be asked to disclose genetic test findings that may result in the participant: Losing health insurance coverage Other family members losing their health insurance Losing his/her job NOTE: Federal and state laws are supposed to protect against such outcomes, but they are imperfect

74. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 74 Genetic Information Nondiscrimination Act of 2008 (GINA), a Federal law Prohibits discrimination in health coverage and employment based on genetic information generally prohibits health insurers or health plan administrators from requesting or requiring genetic information of an individual or the individual’s family members, or using it for decisions regarding coverage, rates, or preexisting conditions. The law also prohibits most employers from using genetic information for hiring, firing, or promotion decisions, and for any decisions regarding terms of employment

75. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 75 How Might My Tribe or Other Native Americans by Harmed by My Participating in Genetic Testing? Tribal ordinances against participating in “genetic research” (genetic testing may be included in genetic research) “Genetic testing” is an individual decision, there should be little opportunity for harm to the Tribal community

76. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 76 Native American Cultural and Ethical Issues related to Genetic Testing NOTE: Due to projects such as HGDP targeting Aboriginal Peoples, communities are suspicious of any program involving “genetics” Native people being encouraged to take part in genetic testing by being given rewards... without being told the risks of genetic tests.

77. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 77 Native American Cultural and Ethical Issues related to Genetic Testing Native people being tested without being given enough information to make an “informed” decision Native people being tested without having their rights to privacy and confidentiality “protected” Native people being tested without having test results clearly explained (no genetic counseling)

78. Objective 4: Discuss the benefit of recording your family health history slides from NACI GENA® objective 22 (used with permission from Linda B) 78

79. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 79 Reasons Family Histories May be Important Accurate Family Histories are needed to determine if a cancer risk is likely to be hereditary or from other causes (daily behaviors, exposure to environmental contamination) Helps the genetic counselor work with the patient to decide whether or not the patient is genetically at high risk for a condition and should have a genetic test (most cancer genetic tests are expensive)

80. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 80 Reasons Family Histories May be Important (cont.) Helps the provider make a diagnosis Clarifies daily behaviors versus inherited risks for people who are adopted May reveal patterns of inheritance within the family Clarifies family myths regarding who in the family is at risk Helps explain why some members of the family are not affected

81. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 81 1.Name 2.Date 3.Age 4.Ethnic Background 5.Do you have any specific concerns about cancer in yourself or your family? 6.Do you or any members of your family have a history of cancer? Sample Cancer Family History Questionnaire

82. Yes / No Type of Cancer (if known) Age at Dx Living / Deceased yourself your mother your father your sisters & brothers your children your mother's sisters & brothers your father's sisters and brothers your nieces & nephews your mother's parents your father's parents 82

83. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 83 Example of Culturally Inappropriate Family History Data Collection by Epidemiologists during the Hanta Virus Infection CDC scientists demanded to interview the surviving family members immediately following the patient’s death Researchers unaware / unwilling to be educated by local Native physician of local cultural beliefs requiring no discussion of the deceased for 3 days

84. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 84 Example of Culturally Inappropriate Family History Data Collection by Epidemiologists during the Hanta Virus Infection Family forced to violate cultural practices = very difficult ceremony Researchers given inaccurate information Alienated the local AI community Video Role Play of poor family history collection Video role Play of good family history collection

85. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 85 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 85 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 85 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 85 Great Grandparents LEGEND  (square) = male  (circle) = female  (diamond) = sex unknown Dx with a number = age at time of diagnosis / (Diagonal) through symbol means “died” / / (double diagonal) = gap or missing info d. = age at the time of death Parents Grandparents Hyperlink to hereditary breast files

86. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 86 Translate the Family History Definitions QUESTION 1: What does the circle mean? QUESTION 2: What does the square mean? QUESTION 3: What does it mean when a diagonal line goes through the circle or the square? QUESTION 4: What does the “Dx” mean? Female Male Deceased Age of Diagnosis

87. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 87 Translate the Family History Definitions QUESTION 5: What does it mean when part of the circle or square includes a blackened square? QUESTION 6: What does the “d.” mean? QUESTION 7: What does the arrow mean? QUESTION 8: What does it mean when a diamond shape is used? Cancer diagnosed Died The individual providing the information about the family (consultant) Gender unknown

88. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 88 Family History Data Collection Cautions Asking the patient and/or family members personal information about their ancestors and immediate family Some tribes are prohibited from discussing family members who have “walked on” / “passed away” / died Cannot use their name Cannot refer to them directly via relationship (“mother”, “father”)

89. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 89 Family History Data Collection Cautions Violations of these cultural practices can result in the family having to do timely and expensive ceremonies Linear format of family / Family History collection process frequently results in erroneous information Encourage patient to “tell a story” Be careful about how we talk about our relatives (“my daughter”)

90. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 90 “First Degree Relative” vs. Indian Adoption Note: some tribes use maternity for tribal affiliation rather than paternity Cancer risk genetic tests typically focus on first degree relatives (FDRs) Mother, Father Sisters, Brothers Children Spiritually, adopted children are regarded as FDR by AIANS, but NOT so for genetic family trees … question: “did you come from the same womb as your brother?”

91. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 91 “First Degree Relative” vs. Indian Adoption Indian cultures actively support adoption of others who need or want assistance / guidance Cousins, aunties, uncles, other relatives Other members / children / youth of the community Friends / their children / youth

92. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 92 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 92 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 92 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 92

93. Family History and BRCA2 Scenario

94. 94 Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer Initiatives, Incorporated (NACI) 94 Family History Craig Age 42 Prostate problems Dx Ovarian Age 35 Mary Lou Dx BC Age 29 BRCA2 Cathe- rine Age 31 No BRCA2 YOU Age 30 D. Age 45 Turtle Mountain Chippewa Canadian Aboriginal Metis

95. Summary / Take Home Messages 95

96. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 96 Summary; Take Home Messages The most common risks for developing cancer are daily behaviors (diet, exercise, tobacco exposure, alcohol excess) Our ancestors understood genetics very well (that is why we have marriage rules) New scientific words are used to describe much more detailed (molecular / genetic) levels of genetics “Chromosomes”, “genes” and “markers” are common words in the News today

97. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 97 Summary: Take Home Messages Healthy body (somatic) cells are damaged by daily behaviors or sometimes by exposure to environmental contaminants The same cells are injured 5-10 times before the cells begin to become cancer Researchers are using the new, detailed genetic and molecular information to tailor cancer treatments Some of these treatments are available already (e.g., colon, melanoma)

98. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 98 Summary: Take Home Messages Information collected during your family history can help the researchers understand your genetic or molecular information better Collecting family histories in Indian Country is challenging, in part because: Some tribal cultures prohibit the use of family relations who have passed on (e.g., you cannot say, “father” or “sister”)

99. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 99 Summary: Take Home Messages Most of our tribal Nations practice casual adoption of nieces, neighbors and others who need a home Once adopted, they are of our family spiritually … we do not distinguish siblings as coming from the same womb, but spiritually we are sisters

100. Post-Session Knowledge 6 Items

101. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Which has the biggest / greatest impact on cancer risks for most people? 1.Exposure to radiation 2.Characteristics inherited from your mom and dad 3.Exposure to environmental contaminants 4.Daily lifestyles (diet, exercise, tobacco use) 5.Don’t know / Not sure

102. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Which is TRUE about chromosomes? 1.Are packed with thousands of genes 2.Are all the same size in humans 3.Are only in a few types of human cells 4.Are located in mature red blood cells 5.Don’t’ know / Not sure

103. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Which is TRUE about BRCA2? 1.Is a large gene (many base pairs) on the 13 th chromosome 2.Is responsible for ~25% of all breast cancers 3.Has no effective cancer treatments to control or manage the disease 4.Is only found in females 5.Don’t’ know / Not sure

104. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Obj 2 – Which chromosome is the largest? 1.22 2.16 3.12 4. 5 5.Don’t know / Not sure

105. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Obj 7 - How would you refer to the short arm of chromosome 3? 1.3Cp0 2.3q 3.3mRNA 4.3p 5.Don’t know / Not sure

106. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Obj 5 / 19 - What type(s) of community approval are required for a research project to be conducted in an American Indian community? 1.Academic approval 2.Community / tribal institutional review board (IRB) 3.Traditional Indian healer’s blessing 4.Tribal college approval 5.Don’t know

107. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Obj 16 -- What do Cytochrome p-450 enzymes do? 1.Cause obesity in American Indians eating traditional diet 2.Make the drug “warfarin” 3.Influence the metabolism of about ½ of all medications 4.Help scientists clone animals and body organs 5.Don’t know / Not sure

108. Session Evaluation 4 Items (you won’t see the results on the screen)

109. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; E_undrst1a Overall, this session was understandable to me. 1.I strongly agree 2.I agree 3.I don’t agree 4.I strongly disagree 5.I don’t want to answer

110. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Overall this session provided useful information to me. 1.I strongly agree 2.I agree 3.I don’t agree 4.I strongly disagree 5.I don’t want to answer

111. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Overall, the quality of the information was appropriate for me 1.I strongly agree 2.I agree 3.I don’t agree 4.I strongly disagree 5.I don’t want to answer

112. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Would you recommend this workshop to your friends or colleagues (who already have general knowledge about cancer)? 1.Yes 2.Maybe 3.No 4.Not Sure

113. Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; 113 Thank you for allowing us to share Native Cancer 101 module with you

114. 3 = History 6 = Intelligence 10 = Cortisol and Stress 11 = Personality 12 = ability to dev human body from a fertilized egg 13 = BRCA 2 14 = telomeres15 = SexSlide 108 16 = learning 17 = ApoptosisSlide 109 18 = gene therapy 19 = cholesterol 20 = PRPSlide 110 21 = Down’s Syndrome 22= HFW and “Free Will” Y = maleX = female 4 = Fate2 = Species 1 = Life5 = Environment 8 = Self- Interest 7 = Instinct 9 = ABO Blood Group 114

115. Example of Chromosome 1 = Life; gene for lactase that is necessary to digest lactose, a sugar abundant in milk; most humans are born with this gene switched on in their digestive systems. The gene turns off and adults may have difficulty digesting lactase. One way around the problem is to let bacteria digest the lactose and turn the milk into cheese. Cheese, being low in lactose, is easily digestible for adults and children. A mutation in the control gene that switches off the lactase gene results in people who can drink and digest milk all through life. More than 70% of western Europeans by descent can drink milk as adults, compared with less than 30% of people from parts of Africa, eastern and southeastern Asia and Oceania (Ridley, p. 193)

117. Example of chromosome 10 = CYP 17 enables the body to convert cholesterol into cortisol, testosterone and oestradiol. Cortisol interferes with the immune system, changes sensitivity of the ears, nose and eyes, and alters various bodily functions. When you have a lot of cortisol, you are “under stress”. Cortisol and Stress are synonymous (Ridley, p. 149). Because cortisol interferes with the immune system when under stress, a person is more likely to “catch a cold” or other infections. Cortisol does this by reducing the activity, number and lifetime of lymphocytes (white blood cells)

118. Example of Chromosome 11 = Personality; The D 4 DR gene is one of the brain’s dopamine-mediated pathways. Dopamine pathways control the flow of blood through the brain. A shortage of dopamine in the brain causes an indecisive and frozen personality, unable to initiate even the body’s own movement… in the extreme = Parkinson Disease. An excess of dopamine = highly exploratory and adventurous or related to Schizophrenia. Too little dopamine and the person lack initiation and motivation; Too much and the person is easily bored & frequently seeks new adventures. (Ridley, p. 163)

119. Example of Chromosome 14 = Immortality; TEP1 telomerase (top of the chromosomes) contains RNA which rebuilds telomeres (Ridley, p. 197) Note: Dolly the sheep’s descendents grow up “older” than other sheep

120. Examples of Chromosome 15 genes = Sex-related anomalies from missing chunks of chromosome from one of the parents Prader-Willi Syndrome: children born floppy and pale-skinned; refuse to suck at the breast, but later eat till they almost burst … never experiencing satiety; Or the opposite, Angelman’s syndrome: children born taut; thin, hyperactive, insomniac, small-headed, long-jawed, move jerkily; often stick out large tongues; BUT have happy dispositions, smiling and frequent outbursts of laughter (Ridley, p. 207). They never learn to speak; severely mentally retarded

121. Example(s) of Chromosome 17 genes = ced-9 or gene that helps old cells die (Apoptosis) Oncogenes and cancer Tumor suppressor genes turned off = cancer Gene that tells cells to commit suicide is TP 53 which makes p53. A mutation in TP53 is related to cancer (55% of all human cancers have damage to TP53 and 90% of all lung cancers have damage to TP53 ). (Ridley, p. 236) People born with one faulty version of TP53 out of the two they inherit have a 95% change of getting cancer and usually at an early age. Lynne calls p53, “the big guy” for this reason Colorectal cancer and APC and/or ras related to polyps

122. 122 NACI’s Edited Background Information BRCA2 Summary Fact Sheet Discovered: 1995 Location 13q12 Very large gene Tumor suppressor Genetics: Autosomal dominant transmission of germline alteration (mutation) Transmission of germline mutation by EITHER parent 122

123. 123 NACI’s Edited Background Information BRCA2 Summary Fact Sheet (cont.) Germline mutation increases RISK for breast and ovarian cancers Cancer is a progressive process of different mutations that alter cell function. Eventually, cell function is altered so much that it becomes “cancerous”. 123

124. 124 NACI’s Edited Background Information BRCA2 Summary Fact Sheet (cont.) An inherited susceptibility to cancer, like a germline mutation in BRCA2 gene, means that a person has inherited a “damage” which decreases the number of further acquired mutations needed for a cell to become cancerous. i.e., most “cancer” evolves after at least “two” damages 124

125. 125 NACI’s Edited: Increased Cancer Risks for Mutations in BRCA2: Women Breast cancer Ovarian cancer (not as high as BRCA1 mutations) Men Breast cancer Prostate cancer

126. 126 NACI’s Edited Increased Cancer Risks for Mutations in BRCA2: Other Cancers (risk for these may be slightly elevated over the general population) Colon cancer Pancreatic cancer Stomach cancer Cancer of the gallbladder Melanoma