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
Lanyard that goes around your neck Turning Point Keypads
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.
3.
Female Don’t want to answer
43% 57% 1 2 0% 3
About How Old are You?
1.
81 and older 2.
65-80 3.
50-64 4.
41-49 5.
31-40 6.
21-30 7.
8.
9.
13-20 Under 12 Don’t want to answer
1 0% 29% 2 43% 3 14% 4 0% 5 14% 6 0% 7 0% 8 0% 9 brthyr5
What is Your Primary Race?
1.
43%
American Indian / Alaska Native (AIAN) 2.
Pacific Islander 3.
Asian 4.
African-American 5.
6.
7.
Non-Hispanic white (Caucasian)
0% 0%
Other
1 2 3
Don’t know / Don’t want to answer
0% 4 43% 5 0% 6 14% 7
How Much Schooling have You Completed?
1.
2.
3.
4.
Elementary (kindergarten through grade 6 / grade school)
29% 29%
7 th , 8 th , or 9 th grade (middle school) 10, 11, or 12 th grade (no degree) High school graduate / GED 5.
6.
Technical school /apprentice training Some college (no degree) 7.
8.
9.
College AA degree College BA, BS degree Masters’ degree 10.
Doctorate or more
0% 1 0% 2 0% 3 4 14% 5 6 0% 7 14% 8 14% 9 0% 10
3 Pre-Session Knowledge Items
Which has the biggest / greatest impact on cancer risks for most people?
1.
2.
3.
4.
5.
Exposure to radiation Characteristics inherited from your mom and dad Exposure to environmental contaminants Daily lifestyles (diet, exercise, tobacco use) Don’t know / Not sure
29% 71% 0% 1 0% 2 3 4 0% 5
Which is TRUE about BRCA2?
1.
2.
3.
4.
5.
Is a large gene (many base pairs) on the 13 th chromosome Is responsible for ~25% of all breast cancers Has no effective cancer treatments to control or manage the disease Is only found in females Don’t’ know / Not sure
71% 14% 1 14% 2 0% 3 0% 4 5
Obj 2 –
Which chromosome is the largest?
1.
2.
3.
4.
5.
22 16 12 5 Don’t know / Not sure
71% 29% 0% 1 0% 2 0% 3 4 5
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;
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;
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;
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;
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;
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;
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;
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;
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;
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;
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;
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;
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, 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
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;
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;
Post-Session Knowledge 3 Items
Which has the biggest / greatest impact on cancer risks for most people?
100%
1.
2.
3.
4.
5.
Exposure to radiation Characteristics inherited from your mom and dad Exposure to environmental contaminants Daily lifestyles (diet, exercise, tobacco use) Don’t know / Not sure
0% 0% 0% 1 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;
3 4 0% 5
Which is TRUE about BRCA2?
86%
1.
2.
3.
4.
5.
Is a large gene (many base pairs) on the 13 th chromosome Is responsible for ~25% of all breast cancers Has no effective cancer treatments to control or manage the disease Is only found in females Don’t’ know / Not sure Northwest Portland Area Indian Health Board;
1 0% 2 14% 3 0% 4 0% 5
1.
2.
3.
4.
5.
22
Obj 2 –
Which chromosome is the largest?
16 12 5 Don’t know / Not sure
100% 0% 0% 0% 1 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;
3 4 0% 5
Session Evaluation
2 Items (you won’t see the results on the screen)
Overall, this session was understandable to me.
1.
I strongly agree 2.
3.
I agree I don’t agree 4.
5.
I strongly disagree I don’t want to answer
86% 14% 2 0% 3 0% 4 0% 5 1
Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board;
E_undrst1a
Overall this session provided useful information to me.
1.
I strongly agree 2.
3.
I agree I don’t agree 4.
5.
I strongly disagree I don’t want to answer
71% 29% 1 2 0% 3 0% 4 0% 5
Bemis, UMN-Duluth, Burhansstipanov, Native American Cancer Initiatives, Incorporated (NACI) Mayo Clinic’s “Spirit of EAGLES Community Network Programs 2” [P.I. Kaur; U54CA153605] ; Northwest Portland Area Indian Health Board;
Thank you for allowing us to share Native Cancer 101 module with you
45
2 = Species 3 = History
5 = Environment 6 = Intelligence 7 = Instinct 8 = Self Interest
Group
12 = ability to dev human body from a fertilized egg 18 = gene therapy 13 =BRCA
2
19 = cholesterol
16 = learning
21 = Down’s Syndrome 22=HFW and “Free Will” Y = male
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 =
CYP 17
enables the body to convert cholesterol into cortisol, testosterone and oestradiol. Cortisol interferes with the immune system, changes sensitivity of the ears, nose and eyes, and alters various bodily functions. When you have a lot of cortisol, you are “under stress”. Cortisol and Stress are synonymous (Ridley, p. 149). Because cortisol interferes with the immune system when under stress, a person is more likely to “catch a cold” or other infections. Cortisol does this by reducing the activity, number and lifetime of lymphocytes (white blood cells)
Example of Chromosome 11 =
Personality; The D
4
DR gene is one of the brain’s dopamine-mediated pathways. Dopamine pathways control the flow of blood through the brain. A shortage of dopamine in the brain causes an indecisive and frozen personality, unable to initiate even the body’s own movement… in the extreme = Parkinson Disease.
An excess of dopamine = highly exploratory and adventurous or related to Schizophrenia. Too little dopamine and the person lack initiation and motivation; Too much and the person is easily bored & frequently seeks new adventures. (Ridley , p. 163)
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 56
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