Download “Genes” and “Mutations” - Native American Cancer Research

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
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
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 biobanks and
biospecimens.
The workshop facilitator / faculty is/are
NOT interested to collecting biospecimens
from you.
Introduction and
overview
3
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;
4
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
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;
5
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.
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;
6
Objective 1:
Define basic genetics
terminology
genes, chromosomes,
DNA, mutation, heredity
7
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;
8
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;
9
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
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;
10
“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
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;
11
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)
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;
12
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;
13
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
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
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;
15
Objective 2: Describe
role of genes in cancer
16
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;
17
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
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;
18
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
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
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)
20
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
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
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
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
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?
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
Oncogenes and Adapted Cancer
Treatments
Oncogenes are genes that are overexpressed, 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.
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
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
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
Researchers Study Molecular Pathways
Researchers study
Epidermal
Growth Factor
“pathways” for how
EGF Binds to
(EGF)
Receptor
oncogenes reach the
EGF
cancer tumor cells
Receptor
Growth
Signal
These are molecular
pathways that tell the Pathway
tumor cell to grow grow Nucleus
Cell growth
grow (also called
“amplification”)
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
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
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
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
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;
28
cetuximab
Epidermal Growth Factor
Epidermal
Growth
EGF Binds to
Receptor EGFR is a
Factor
Receptor
receptor on the cell’s
(EGF)
EGF
Receptor
Growth
surface
Signal
Found on many cancer Pathway
cells (lung, CRC)
Nucleus
Cell growth
The EGFR protein gives
improper signals to the
tumor cell to grow grow grow
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
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
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
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
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
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
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
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
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
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)
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
Objective 3: Describe
potential benefits and
drawbacks of genetics
testing
35
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
36
Using BRCA2 As An Example
Populations
BRCA2
who may carry
mutation(s)
the mutation
Ashkenazi
Jewish
6174delT
Dutch
5579insA
French
Canadians
8765delAG
Result of the mutation
A deletion of a T base results
in a shorter than normal
protein
An extra base (A) causes
altered expression of the
protein
In this case two base pairs
are missing
37
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
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;
38
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;
39
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;
40
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;
41
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”
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;
42
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
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;
43
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
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;
44
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
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;
45
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
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;
46
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.
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
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)
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
Objective 4: Discuss the
benefit of recording
your family health
history
slides from NACI GENA® objective 22
(used with permission from Linda B)
49
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)
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
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
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
Sample Cancer Family History Questionnaire
1.
2.
3.
4.
5.
Name
Date
Age
Ethnic Background
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?
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
Yes /
No
Type of
Cancer
Age at
Dx
Living /
Deceased
(if known)
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
53
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
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
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
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;
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Great Grandparents
Grandparents
Parents
LEGEND
 (square) = male
 (circle) = female
(diamond) = sex unknown
Dx with a number = age at time of diagnosis
Bemis, UMN-Duluth,
Mayo
Burhansstipanov,
Clinic’s “Spirit ofNative
EAGLES
American
Community
CancerNetwork
Initiatives,
Programs
Incorporated
2” [P.I.(NACI)
Kaur;
/ (Diagonal)
through
symbol
means
“died”
Mayo Clinic’sU54CA153605]
“Spirit of EAGLES
; Northwest
Community
Portland
Network
AreaPrograms
Indian Health
2” [P.I.
Board;
Kaur;Native
U54CA153605]
American Cancer
;
/ / (double diagonal) =Northwest
gap orPortland
missing
info
Initiatives,
Area Indian
Incorporated
Health Board;
(NACI)
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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”)
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
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”)
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
“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?”
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
“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
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
Summary / Take Home
Messages
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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
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;
62
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;
63
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”)
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;
64
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
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;
65
Thank you for
allowing us to share
Native Cancer 101
module with you
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;
66
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
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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”.
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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
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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
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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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