Transcript Slide 1

Native Cancer 101
Module 4: Role of Genes in Cancer
Kathleen Ragan, BS, CHES
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
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
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
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)
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;
4 Demographic items
(TP)
What is your gender?
1. Male
2. Female
3. Don’t want to answer
57%
43%
0%
1
2
3
About How Old are You?
1.
2.
3.
4.
5.
6.
7.
8.
9.
81 and older
65-80
50-64
41-49
31-40
21-30
13-20
Under 12
Don’t want to answer
43%
29%
14%
0%
1
14%
0%
2
3
4
5
6
0%
0%
0%
7
8
9
brthyr5
What is Your Primary Race?
43%
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
1
43%
14%
0%
0%
0%
2
3
4
0%
5
6
7
How Much Schooling have You Completed?
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
29%
29%
14%
0%
0%
0%
1
2
3
14%
14%
0%
4
5
6
7
0%
8
9
10
3 Pre-Session
Knowledge Items
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
Which is TRUE about BRCA2?
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 –
1.
2.
3.
4.
5.
Which chromosome is the
largest?
22
16
12
5
Don’t know / Not
sure
Introduction and
overview
13
Examples of Genetic Traits
Tongue rolling
Hand clasp
Ear lobes
Arm folding
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;
14
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
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;
15
Genetics is not new information for AIANs
The concept of genetics is not new, but:
How genetics is being used 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
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;
16
QUESTION: Why is this important for
AI/AN communities?
Cancer = increasing 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.
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;
17
Objective 1:
Define basic genetics
terminology
genes, chromosomes,
DNA, mutation, heredity
18
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
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;
19
Chromosomes
Organized by
researchers from
the largest /
longest (number
1) to the smallest
(number 22).
The longer the
chromosome, the
more genes
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;
20
“Genes” and “Mutations”
The pattern of information within genes needs
to follow a specific sequence for the cell to
function correctly (ex. stack of bread).
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
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;
21
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
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;
22
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
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;
23
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
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;
24
Role of genes: mutations (continued)
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
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;
25
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
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
Objective 3: Describe
potential benefits and
drawbacks of genetics
testing
27
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
28
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)
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;
29
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
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
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
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
Possible Drawbacks to Genetic Testing
Genetic “mutation” may be present, but
there may not be a “treatment”
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
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
Reasons Family Histories May be
Important
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
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
Bemis, UMN-Duluth,
Mayo
Burhansstipanov,
Clinic’s “Spirit ofNative
EAGLES
American
Community
CancerNetwork
Initiatives,
Programs
Incorporated
2” [P.I.(NACI)
Kaur;
Mayo Clinic’sU54CA153605]
“Spirit of EAGLES
; Northwest
Community
Portland
Network
AreaPrograms
Indian Health
2” [P.I.
Board;
Kaur;Native
U54CA153605]
American Cancer
;
Northwest Portland
Initiatives,
Area Indian
Incorporated
Health Board;
(NACI)
34
34
34
Summary / Take Home
Messages
35
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
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
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)
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
Post-Session
Knowledge
3 Items
Which has the biggest / greatest impact
on cancer risks for most people? 100%
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
0%
1
0%
2
0%
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;
3
0%
4
5
Which is TRUE about BRCA2?
86%
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
14%
treatments to control or
manage the disease
0%
4. Is only found in females
1
2
3
Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI)
5. Mayo
Don’t’
know
Not sure
Clinic’s “Spirit
of EAGLES/Community
Network Programs 2” [P.I. Kaur; U54CA153605] ;
Northwest Portland Area Indian Health Board;
0%
4
0%
5
Obj 2 –
1.
2.
3.
4.
5.
Which chromosome is the
largest?
22
16
12
5
Don’t know / Not
sure
0%
1
0%
2
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;
100%
0%
3
0%
4
5
Session Evaluation
2 Items
(you won’t see the results on the
screen)
Overall, this session was understandable
to me.
1.
2.
3.
4.
5.
I strongly agree
I agree
I don’t agree
I strongly disagree
I don’t want to
answer
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 provided useful
information to me.
1.
2.
3.
4.
5.
I strongly agree
I agree
I don’t agree
I strongly disagree
I don’t want to answer
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;
Thank you for
allowing us to share
Native Cancer 101
module with you
45
1 = Life
2 = Species
6 = Intelligence 7 = Instinct
3 = History
4 = Fate
8 = Self- 9 = ABO Blood
11 =
10 = Cortisol
Interest
Group
and Stress Personality
5 = Environment
12 = ability to dev
human body from a
fertilized egg
18 = gene therapy
13 =BRCA2
19 =
cholesterol
14 = telomeres
20 =
PRPSlide
15 =
SexSlide
108
21 = Down’s
Syndrome
16 = learning 17 =
ApoptosisSlide 109
22=HFW and
“Free Will”
Y = male
46
X = female
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 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
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
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
54
54
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”.
55
55
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
56
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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
57
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
58