GenetiKit Workshop Given by: Dr. Sean Blaine, Family Physician Dr. June Carroll, Family Physician Clare Gibbons, Genetic Counsellor Cathy Gilpin, Genetic.

GenetiKit Workshop

Given by: Dr. Sean Blaine, Family Physician Dr. June Carroll, Family Physician Clare Gibbons, Genetic Counsellor

Cathy Gilpin, Genetic Counsellor

Funded by CIHR

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GenetiKit Project Purpose:

To help family physicians think “genetically” To increase knowledge about genetic testing for

common disorders To give family physicians a framework for assessing

the usefulness of new genetic tests

Funded by CIHR

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GenetiKit Project ProtocolStep 1: Questionnaire #1 – already completed

Step 2: Workshop Introduce tools to help integrate genetics into practice - case example

Step 3: Use project tools over next 6 months

Step 4: Questionnaire #2 $250 to compensate for your time at completion of Q2

We want to see: What you think of our project materials Do they help you in practice?

Please do not share this information with your colleagues

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Why is genetics important? Case example GenetiKit toolsStudy protocol

Gene MessengerGenetiKit Web site

Workshop Outline

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By 2010:Predictive genetic tests for a dozen

common conditions“$1000 genome sequencing test”No longer only the domain of geneticists and

genetic counsellors

Genomic medicine will change medical practice

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The Promise of Genetics:

Prediction of risk of diseaseIndividualized screening, surveillance, and

prevention Safer and more effective drug therapyIndividualized environmental risk factor

assessment

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The reality – Is this “genohype”?

Genetic testing available for very few common adult onset hereditary diseases

Gene-environment interaction responsible for most common diseases

Lack of evidence for effective interventions

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Why should family physicians know about genetics?

Common diseasesPublic interestMedia coverage of genetic testingDirect marketing of genetic testingPatients will turn to family physicians

for information and advice

FP’s patients asked: Where would you go for more information about genetic testing?

0 20 40 60 80 100

Surgeon

Magazines

Fam mem

Geneticist

Books

Gen Coun

Cancer Sp

Internet

FP

Carroll, Blaine et al 2002 Unpublished data

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What Makes Genetic Testing for Adult-Onset Diseases Different from Other Types of Testing?

Uncertainty Will the condition develop? When? How severe? Will interventions make a difference?

Direct implications for family members Ethical, legal and social issues

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Case Example - Breast Cancer

35 year old investment banker asked her busy family doctor to refer her for genetic

testing history of breast cancer in grandmother has heard of BRCA testing looked at Myriad website would like genetic testing…..

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Maternal family history

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David

A&W

35 PATIENT A&W

Breast CaDx 72

Breast

Legend

60IreneA&W

58 Jean↑ Chol

30 30Michael JasonA&W A&W

76d. MI

63George

HTN

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Family history assessment

Breast

Legend

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Family history assessment

Breast

Legend

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Family history assessment

Breast

Legend

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Ontario Physician’s Guide to Referral of Patients with a Family History of Cancer to a Familial

Cancer Genetics Clinic or Genetics Clinic

Sources:

MOH 2002 Bulletin

http://www.health.gov.on.ca/english/providers/program/ohip/bulletins/4000/bul4381.html

Ontario Medical Review (Nov 2001)

www.oma.org/pcomm/OMR/nov/01genetics.htm

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Let’s continue the case….

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Pearls – Red flags for hereditary disorders

Multiple affected relativesMore than 1 generation affectedClosely related Early age of onset

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Who should be offered referral for genetic counselling and/or genetic testing?

Multiple cases of breast and/or ovarian cancer in family closely related relatives

more than one generation

Br Ca diagnosed at < age 50

Breast cancer diagnosed at age < 35

Family member with both breast and ovarian cancers

Ashkenazi Jewish + relatives with breast or ovarian cancer

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Who should be offered referral for genetic counselling and/or genetic testing?…

Family member with primary cancer in both breasts

especially if diagnosed < age 50

Family member with invasive serous

ovarian cancer

Male breast cancer

Family member with an identified

BRCA1 or BRCA2 mutation

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Adding paternal family history

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David

A&W

35 PATIENT A&W

Breast CaDx 72

60IreneA&W

58Jean

↑ Chol

30 30Michael JasonA&W A&W

76d. MI

63George

HTNOvarian CaDx ?

Bilateral Breast Ca

Dx ?

BreastOvarian

Legend

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32

David

A&W

35 PATIENT A&W

Breast CaDx 72

60IreneA&W

58Jean

↑ Chol

30 30Michael JasonA&W A&W

76d. MI

63George

HTNOvarian CaDx ?

Bilateral Breast Ca

Dx ?

BreastOvarian

Legend

Diabetes

Paternal family history

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David

A&W

35 PATIENT A&W

Breast CaDx 72

60IreneA&W

58Jean

↑ Chol

30 30Michael JasonA&W A&W

76d. MI

63George

HTNd. 57

Ovarian CaDx 56

Breast

Ovarian

Legend

Diabetes

Bilateral Breast Ca

Dx 45Dx ?

A&W

d. 70’sBreast Ca

Dx 69

90’s

A&W

Paternal family history

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Breast

Ovarian

Legend

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David

A&W

35 PATIENT A&W

Breast CaDx 72

60IreneA&W

58Jean

↑ Chol

30 30Michael JasonA&W A&W

76d. MI

63George

HTNOvarian Ca

Dx 56 Diabetes

Bilateral Breast Ca

Dx 45Dx ?

A&W

90’s

A&W

d. 70’sBreast Ca

Dx 69

Family history

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Family history assessment

Breast

Ovarian

Legend

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bb Bb

Bb bb Bb bb

Breast Cancer

Affected withbreast cancer

Autosomal Dominant Inheritance

Population Risk

Population Risk

SusceptibleBRCA gene

Unaffected

Legend

B: BRCA gene with mutation

b: normal BRCA gene

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Consequences of having a BRCA mutationEstimated Risk in BRCA Mutation

Carriers – by Age 70

In General Population

Breast Cancer ♀ 50 - 85% 11%

Ovarian CancerBRCA1

40-60% 1-2%

Ovarian CancerBRCA2

10-20% 1-2%

Breast Cancer ♂BRCA2

6% <1%

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Breast

Ovarian

Legend

32

David

A&W

35 PATIENT A&W

Breast CaDx 72

60IreneA&W

58Jean

↑ Chol

30 30Michael JasonA&W A&W

76d. MI

63George

HTNOvarian Ca

Dx 56 Diabetes

Bilateral Breast Ca

Dx 45Dx ?

A&W

90’s

A&W

d. 70’sBreast Ca

Dx 69

Family history

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Possible Genetic Testing Results

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Possible Genetic Testing Results

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Possible Genetic Testing Results

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Possible Genetic Testing Results

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What are the benefits / harms

of genetic testing for hereditary breast/ovarian

cancer?

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BENEFITS - Mutation Present

Disease Causing Mutation Present Gene mutation predicted to cause or increase risk

for disease Clinical Benefit

Clear basis for existing clinical interventions that improve outcome

“OK, so I have the gene, what should I do to protect myself and stay healthy?”

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BENEFITS - Mutation Absent

Clear Negative Genetic Test Result Absence of a known gene mutation previously

identified in the family Emotional Benefit

Relief from worry about disease risk “Thank goodness I don’t have it!”

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Benefits

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HARMS – Mutation Present

Disease Causing Mutation Present

Socio-legal Harms Insurance premiums may be increased

Other HarmsFear! Patient may become fatalistic towards health Other family members may become distressed on

patient’s or their own behalf

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HARMS – Mutation Present Variant of Unknown Significance Emotional harm

Uncertainty What does the mutation really mean? How to

handle it? Remember they are still at high risk on the basis of

their family history, so the clinical interventions apply and may carry their own risks

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HARMS – Mutation Absent

Clear Negative gene test result

Emotional harmSurvivor Guilt Cannot identify with the disease group No excuse for life problems

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HARMS - Mutation Absent

Uninformative Test Result

Health Behaviour Harm Complacency Fatalism towards health Still need to follow clinical recommendations as

family history risk still present

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Harms

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What can be done for BRCA Mutation Carriers to reduce the risk of breast/ovarian cancer?

Surgical options - Bilateral risk-reducing mastectomy  

- Bilateral risk-reducing oophorectomy

 - 90% risk reduction in high-risk women  

- hazard ratio for br ca = 0.47 - hazard ratio for ovarian ca = 0.04

Chemoprevention-Tamoxifen- raloxifene, aromatase inhibitors

 - shows promise in BRCA2 carriers- under study

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Genetics clinical pathway Pattern – is it genetic? Known gene mutation(s) for disorder? Evidence for gene mutation = disorder? What proportion of people with the disorder

have the gene mutation? Can we change disease incidence? Can we change disease outcome?

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Genetic Clinic Resources

Talk to your local genetics clinicCheck whether referral appropriateUpdate on new genetic tests or advancements

Contact information in package

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Family Physician’s Role in Genetics

Take a family history Assess risk Refer to genetics Discuss benefits and harms of genetic testing Provide emotional support Coordinate prevention

and management

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GenetiKit Tools Hereditary breast/ovarian cancer triage/management card

+ patient booklet and web site Hereditary crc triage/management card Pearls Ontario Guidelines for referral and testing for hereditary

breast/ovarian and colorectal cancer Family History Tool Consequences tool Gene Messenger Contact sheet for genetic clinic referrals

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Gene MessengerTo suggest topics, email us at:

[email protected]

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GenetiKit Web Site

www.genetikit.com

Password: genetics

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Please fill in the workshop evaluation

Thank you.Questions?