burhansstipanov, native american cancer initiatives, incorporated (naci) mayo clinic’s “spirit...

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

(BASIC Community version)estimated time: 120 minutes with Participant interactivity

05-15-2012 version

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



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)

2

For further information

Spirit of E.A.G.L.E.S.Charlton 6

Mayo Comprehensive Cancer Center200 First Street, S.W.Rochester, MN 55905

Phone: (507) 266-3064 Fax: (507) 266-2478

[email protected]

Kerri Lopez, BANorthwest Portland Area Indian

Health Board2121 SW Broadway, Suite 300

Portland, Oregon 97201Phone: 503-228-4185

Fax: [email protected]

www.npaihb.org

Mayo SoE Native Cancer 101 Working GroupsPaulette A. Baukol, BS Dana Kontras. RN, MSNLinda Burhansstipanov, MSPH, DrPH Kerri Lopez, BA

Scientific Expertise: Lynne T. Bemis, PhD, Chair of Biomedical Sciences Department, University of Minnesota Medical School Duluth

mailto:[email protected]

Please turn off your cell phones or switch

them to “vibrate” mode

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

Introduction and overview



Genetics is not new information for AIANs

Our ancestors knew how to

Grow stronger, more disease-resistant crops (e.g., corn and squash)

Breed horses (Pintos, Appaloosa) so that their coloring blended with rocks, ground or aspens during the winter

©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

Objective 1: Define basic genetics

terminology

genes, chromosomes, DNA, mutation, heredity



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

Chromosomes are packed with thousands of genes

Genes tell our cells what to be and how to act

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 = Sex 16 = learning 17 = Apoptosis

18 = gene therapy

19 = cholesterol

20 = PRP 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



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



More about “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:

No effect on the function of the gene The gene to continue having the normal function



Example: p53 (“The Big Guy”)

The gene to do something different than what it was supposed to do

Human chromosomes have a segment of 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



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)

Interactivity: Chromosome RopesPlease work in pairs

Each envelop has an enlarged, but proportional rope

Please look at the chromosome

What is the number of your 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?

Make a copy of the chromosome you are using from the 2nd envelope (clipped)

In your pairs, please make 2 chromosomes that match the ones provided from the 1st envelopeYou will have a total of 4 rope chromosomes; please return the original 2 in the envelopeEach of you should have a pair of rope chromosomes One of you is from the male (sperm) and the other is from the female (egg)



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



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)

29

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



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?



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

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



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 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



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



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)



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 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



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



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



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

Challenging to distinguish among “blood” relatives and “adopted” relatives via AIAN beliefs

Summary / Take Home Messages



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 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)




• 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”)




– 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



Thank you for allowing us to share the current draft of this Native module

with you

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 lactose. 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)

Some facts about your life depend entirely on a single gene--for example, whether

you'll get the dreadful degenerative disease Huntington's chorea, and if so, at what age

Huntington disease (HD) is a neurodegenerative disorder caused by the addition of nucleotides within the HD gene.

Huntingtin is the name for the very large protein that is disfunctional in HD.

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 lacks initiative

and motivation; Too much and the person is easily bored &

frequently seeks new adventures. (Ridley , p. 163)


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 because they have shorter telomeres so even though they

were baby sheep they had older seeming chromosomes.

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


PRP (protease-resistant protein) and prions that reshape normal prions and how they “fold up”… 1986 and bovine

spongiform encephalopathy … “mad cow disease”

71

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

72

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”.

73

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

74

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

75

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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