bemis, umn-duluth, burhansstipanov, native american cancer initiatives, incorporated (naci) mayo...

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 101Module 4: Role of Genes in Cancer

Intermediate (science students, beginning professionals) versionestimated time: 120 minutes with Participant interactivity

02-02-2013 version with ARS

Linda Burhansstipanov, MSPH, DrPHNative American Cancer Initiatives, Incorporated (NACI)

3022 South Nova Road Pine, CO 80470-7830

http://www.NatAmCancerInitiatives.org

Lynne Bemis, PhD, Head of Biomedical Sciences DepartmentUniversity of Minnesota School of Medicine, Duluth Campus

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.

Please turn off your cell phones or switch them

to “vibrate” mode

Audience Response System (the Keypads)

(TP)


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



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)



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

5 Demographic items(TP)

What is your gender?

1 2 3

33%

0%

67%1. Male

2. Female

3. Don’t want to answer

brthyr5

About How Old are You?

1 2 3 4 5 6 7 8 9

0% 0% 0%

67%

0%0%0%0%

33%

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


What is Your Primary Race?

1 2 3 4 5 6 7

14% 14% 14% 14%14%14%14%

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

Are you Hispanic, Latino or Chicano?

1 2 3 4

25% 25%25%25%1. Yes

2. No

3. Don’t Know / Not sure


How Much Schooling have You Completed?

1 2 3 4 5 6 7 8 9 10

0% 0% 0% 0% 0%0%0%

33%

67%

0%

1. Elementary (kindergarten through grade 6 / grade school)

2. 7th , 8th , or 9th grade (middle school)

3. 10, 11, or 12th 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

Personal Experience

Questions (TP)2 items

How much science education have you completed?

1 2 3 4 5

0%

67%

0%

33%

0%

1. None

2. Between 1-6 hours

3. Between 7-14 hours

4. 15+ hours

5. Don’t know / Don’t want to answer`

Have You ever been Told by a Healthcare Provider that you have Cancer?

1 2 3 4

100%

0%0%0%

1. No

2. Yes

3. Don’t know


5 Pre-Session Knowledge Items

Which has the biggest / greatest impact on cancer risks for most people?

1 2 3 4 5

2%

14%

7%

68%

9%

1. Exposure to radiation 2. Characteristics inherited from

your mom and dad3. Exposure to environmental

contaminants4. Daily lifestyles (diet,

exercise, tobacco use)5. Don’t know / Not sure

Which is TRUE about BRCA2?

1 2 3 4 5

4%

38%

49%

4%4%

1. Is a large gene (many base pairs) on the 13th 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

Obj 2 – Which chromosome is the largest?

1 2 3 4 5

31%

13%

47%

9%

0%

1. 22

2. 16

3. 12

4. 5

5. Don’t know / Not sure

Obj 7 - How would you refer to the short arm of chromosome 3?

1 2 3 4 5

0%

16%

58%

11%16%

1. 3Cp0

2. 3q

3. 3mRNA

4. 3p


Obj 5 / 19 - What type(s) of community approval are required for a research project to be

conducted in an American Indian community?

1 2 3 4 5

0%

84%

11%

2%2%

1. Academic approval2. Community / tribal

institutional review board (IRB)

3. Traditional Indian healer’s blessing

4. Tribal college approval 5. Don’t know

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

Introduction and overview

24



Examples of Genetic Traits

Tongue rolling

Hand clasp

Ear lobes

Arm folding

25



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



Genetics is not new information for AIANs

The concept of genetics is not new, but: How genetics is being used todayNew words created to describe genetic science todayNew cultural issues for protecting privacy of individual and tribal Nations todayNew science that can be generated to help address common health problems (diabetes, cancer) among Natives today...

Those are new ideas and concepts for AIANs



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

Objective 1: Define basic genetics

terminology

genes, chromosomes, DNA, mutation, heredity

29



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 strongOther genes help prevent cancer (tumor suppressor)

A gene is a segment within a chromosome



Chromosomes

Organized by researchers from the largest / longest (number 1) to the smallest (number 22).The longer the chromosome, the more genes



Chromosomes (continued)DNA (Deoxyribonucleic Acid) molecules refer to the genetic information that is within the chromosomesChromosomes are in the “nucleus” (“brains” of the cell)

Chromosomes are packed with thousands of genesGenes tell our cells what to be and how to act



“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



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 cancerp53 is a tumor suppressor

Unless it is damaged (mutation)



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



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



Causes of Cancer

Daily Behavior / Lifestyle (not enough physical activity, unhealthy food, excess alcohol, habitual use of tobacco) = cause changes in genes within body cellsEnvironment (exposure to contaminants, e.g., asbestos) = cause changes in genes within body cellsHeredity (chromosomes from mother and father that created the fertilized egg that resulted in the child)

= only 5-10% of all cancers

Objective 2: Describe role of genes in cancer

38



Role of genes in cancer

Only a small group of mutations directly associated with cancer risk are inherited from the parentsOther (i.e., “most”) mutations are acquired over the life spanMultiple 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



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



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

Interactivity: Chromosome Ropes

Rope chromosomes (100,000 of times larger than actual chromosomes)

TelomereCentromere“Single Nucleotide Polymorphism” (SNP) / mutationp seqment q segment

Longest chromosome =1;Shortest chromosome = 22Germ (sex) cells (2)

42

Interactivity: Chromosome RopesChromosome 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

Interactivity: Chromosome RopesWhere 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


Form pairs with someone who has a chromosome that differs from yoursBased 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 SNPWhat does your made-up SNP do?

45


Together (group of 4), create a new cancer-related SNPWhat does your made-up SNP do?

46



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



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



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?



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.



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



Researchers Study Molecular Pathways

Researchers study “pathways” for how oncogenes reach the cancer tumor cellsThese 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



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



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



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



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



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



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



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



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

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 2nd hereditary breast cancer geneCatherine, 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?

Objective 3: Describe potential benefits and drawbacks of genetics

testing

62

6363

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?

6464

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.

Using BRCA2 As An Example

Having the marker (BRCA2) does not mean you will develop cancerThe marker indicates a predisposition Every single person has a BRCA2 gene, but only a few have a mutationPopulations at risk are on following page

65

Using BRCA2 As An Example

Populations who may carry the mutation

BRCA2 mutation(s)

Result of the mutation

Ashkenazi Jewish

6174delTA deletion of a T base results in a shorter than normal protein

Dutch 5579insAAn extra base (A) causes altered expression of the protein

French Canadians

8765delAGIn this case two base pairs are missing

66



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




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)




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



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



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”




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




You may be asked to disclose genetic test findings that may result in the participant:

Losing health insurance coverageOther family members losing their health insuranceLosing his/her job

NOTE: Federal and state laws are supposed to protect against such outcomes, but they are imperfect



Genetic Information Nondiscrimination Act of 2008 (GINA), a Federal law

Prohibits discrimination in health coverage and employment based on genetic informationgenerally 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



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



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.



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)

Objective 4: Discuss the benefit of recording your family health

history

slides from NACI GENA® objective 22 (used with permission from Linda B)

78



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)



Reasons Family Histories May be Important (cont.)

Helps the provider make a diagnosis Clarifies daily behaviors versus inherited risks for people who are adoptedMay 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



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

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



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



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



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)

85Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board; Native American Cancer




85

85

Great Grandparents

LEGEND (square) = male (circle) = female(diamond) = sex unknownDx with a number = age at time of diagnosis/ (Diagonal) through symbol means “died”/ / (double diagonal) = gap or missing infod. = age at the time of death

Parents

Grandparents

Hyperlink to hereditary breast files



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



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



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”)



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”)



“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?”



“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

92

Family History and BRCA2 Scenario





94

Family History

Craig

Age 42Prostate problems

Dx OvarianAge 35

Mary Lou

Dx BCAge 29

BRCA2

Cathe-rine

Age 31No BRCA2

YOU

YOUAge 30

D. Age 45

Turtle Mountain Chippewa Canadian Aboriginal Metis

Summary / Take Home Messages

95



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



Summary: Take Home Messages

Healthy body (somatic) cells are damaged by daily behaviors or sometimes by exposure to environmental contaminantsThe same cells are injured 5-10 times before the cells begin to become cancerResearchers are using the new, detailed genetic and molecular information to tailor cancer treatmentsSome of these treatments are available already (e.g., colon, melanoma)




Information collected during your family history can help the researchers understand your genetic or molecular information betterCollecting 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”)




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

Post-Session Knowledge

6 Items



Which has the biggest / greatest impact on cancer risks for most people?

1 2 3 4 5

20% 20% 20%20%20%

1. Exposure to radiation

2. Characteristics inherited from your mom and dad

3. Exposure to environmental contaminants

4. Daily lifestyles (diet, exercise, tobacco use)




Which is TRUE about chromosomes?

1 2 3 4 5

20% 20% 20%20%20%

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



Which is TRUE about BRCA2?

1 2 3 4 5

20% 20% 20%20%20%

1. Is a large gene (many base pairs) on the 13th 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



Obj 2 – Which chromosome is the largest?

1 2 3 4 5

20% 20% 20%20%20%1. 22

2. 16

3. 12

4. 5




Obj 7 - How would you refer to the short arm of chromosome 3?

1 2 3 4 5

20% 20% 20%20%20%1. 3Cp0

2. 3q

3. 3mRNA

4. 3p




Obj 5 / 19 - What type(s) of community approval are required for a research project to be

conducted in an American Indian community?

1 2 3 4 5

20% 20% 20%20%20%

1. Academic approval

2. Community / tribal institutional review board (IRB)

3. Traditional Indian healer’s blessing

4. Tribal college approval

5. Don’t know



Obj 16 -- What do Cytochrome p-450 enzymes do?

1 2 3 4 5

20% 20% 20%20%20%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


Session Evaluation

4 Items

(you won’t see the results on the screen)


Northwest Portland Area Indian Health Board; E_undrst1a

Overall, this session was understandable to me.

1 2 3 4 5

20% 20% 20%20%20%

1. I strongly agree

2. I agree

3. I don’t agree

4. I strongly disagree

5. I don’t want to answer



Overall this session provided useful information to me.

1 2 3 4 5

20% 20% 20%20%20%

1. I strongly agree

2. I agree

3. I don’t agree





Overall, the quality of the information was appropriate for me

1 2 3 4 5

20% 20% 20%20%20%

1. I strongly agree

2. I agree

3. I don’t agree





Would you recommend this workshop to your friends or colleagues (who already have general knowledge about cancer)?

1 2 3 4

25% 25%25%25%

1. Yes

2. Maybe

3. No

4. Not Sure



Thank you for allowing us to share Native Cancer 101 module with you

3 = History

6 = Intelligence 10 = Cortisol and Stress

11 = Personality

12 = ability to dev human body from a

fertilized egg

13 =BRCA2 14 = telomeres 15 = 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 = male X = female

4 = Fate2 = Species1 = Life 5 = Environment

8 = Self-Interest

7 = Instinct 9 = ABO Blood Group

114

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)

Example of chromosome 10 =

CYP17 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)

Example of Chromosome 11 = Personality; The D4DR 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)

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

Examples of Chromosome 15 genes = Sex-related anomalies from missing chunks of chromosome from

one of the parentsPrader-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

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 reasonColorectal cancer and APC and/or ras related to polyps

122

NACI’s Edited Background InformationBRCA2 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

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123

NACI’s Edited Background InformationBRCA2 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”.

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124

NACI’s Edited Background InformationBRCA2 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

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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

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

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