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Cancer Answers is a series of free public lectures,
presented by Cancer Care Nova Scotia, on a variety of
cancer-related topics. The lectures, delivered by cancer
experts, are designed to raise awareness and educate
participants about issues related to prevention, screening,
early diagnosis, treatment, survivorship and palliative care.
Following each lecture, the presentations are posted on the
Cancer Care Nova Scotia website.
Hereditary Cancer
and
Genetic Testing
Cancer Answers
Cancer Care Nova Scotia
May 20th, 2008
Patricia Steele, MSc, CCGC, CGC
Genetic Counsellor
Maritime Medical Genetics Services
IWK Health Centre
Outline
Cell Growth and Development
 Sporadic, Familial and Hereditary
 Quick Genetics Review
 Common Inherited Forms of Cancer
 Genetic Assessment
 Pros and Cons of Genetic Testing
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Cell Growth and Development
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Many processes control cell growth and cell
division
Cell division – making an exact copy of itself
DNA content doubled and then divided into
both cell copies
Many genes involved
Cancer – Abnormal Cell Growth
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Cancer is the abnormal growth
of cells during cell division
Cancer results from defects or
damage in genes (DNA)
involved in cell division
Several of these controls need
to be damaged before a cell
becomes cancerous
Cancer: When is it Inherited?
~ 85% Sporadic (by chance)
~ 10% Familial
~ 5% Hereditary
Familial~10%
Sporadic ~85%
Hereditary ~5%
Sporadic Cancer History
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Occurs by chance alone
1 or 2 individuals at typical
age of onset
Not an inherited pattern
Relatives usually not at
increased chance to
develop cancer (general
population chance)
Genetic testing not
beneficial
Familial Cancer History
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Not the same type of cancer
or related cancers
Average age of onset
No clear pattern of
inheritance
May be due to shared factors
(genes/environment/lifestyle)
Relatives have slightly
increased chance of cancer
Genetic testing not beneficial
Hereditary Cancer History
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Many family members with
the same or related cancers
Earlier ages of onset
One person may have more
than one type cancer
Two or more generations
affected
Genetic testing may be
beneficial
Quick Genetic Review
The genome is like an
encyclopedia...
A Gene is Like A Recipe for
Making A Specific Protein
Everyone Has Changes
In Their DNA
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Some changes have no
medical effect
A harmful change in the
DNA is called a ‘mutation’
Mutations prevent the
gene from working properly
Some Gene Mutations Cause A
Loss of Function of the Gene
Tumor suppressor genes
instruct the cells to stop
cell division
A mutation in a tumour
suppressor gene is like
having the brakes fail in
your car
Some Gene Mutations Cause A
Gain of Function of the Gene
Oncogenes -initiate
cellular division
(promote cell growth)
A mutation in an oncogene
can speed up cell growth
Like pressing on the gas
peddle of a car all the
time (out of control)
Some Genes Repair DNA Errors
(The DNA Mechanics)
Many Cellular Changes Involved
Inherited or Acquired
Gene Mutations
Dominant Inheritance
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does not cause cancer
increases risk for developing cancer
Inherited Cancer Syndromes
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Hereditary component in ~ 5-15% of these
very common types of cancers
 Colorectal Cancer
 Breast/Ovarian Cancer
Less common inherited cancer syndromes
 Hereditary Diffuse Gastric Cancer
(HDGC)
 Multiple Endocrine Neoplasia (MEN)
 Li-Fraumeni syndrome
 Von Hippel Lindau syndrome
Inherited Colon Cancer
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Hereditary nonpolyposis colon cancer
(HNPCC)
Familial adenomatous polyposis (FAP)
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~ 1% of hereditary colon cancer
Attenuated FAP (later age onset)
MYH Associated Polyposis (MAP)
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~ 1% of hereditary colon cancers
Hereditary Nonpolyposis
Colon Cancer (HNPCC)
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Small number of polyps
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Many DNA repair genes involved
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Also called Lynch syndrome
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Type 1– Colon cancer
Type 2 Colon
 Uterine, breast, pancreas, ovarian, bile duct
Familial Adenomatous Polyposis
(FAP)
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~1% hereditary colon cancers
Hundreds of polyps
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If no treatment – v. high likelihood of cancer
Attenuated FAP (AFAP)
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Onset of polyps - teen years
Start screening no later than age 10
Average age of cancer diagnosis – age 38
multiple polyps
Later age onset of colon cancer (<60 years)
APC gene - good detection rate (~80-90%)
MYH-Associated Polyposis (MAP)
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Families with multiple polyps (like AFAP)
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2002 - new gene found – MYH
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But do not identify APC gene mutation
~10% of AFAP-like families
Screening beginning in 20’s
Recessive inheritance
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inherit 2 non-working genes
See in siblings
Routine Screening ?
Increased Screening?
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Most people:
 ~ 5-6% lifetime chance of colon cancer
 Later ages of onset
 > 10 years from polyp to bowel cancer
If no family history of colon cancer then general population
screening is appropriate
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Colon screening after age 50
Fecal Occult Blood Test (FOBT)
If family history or inherited predisposition then more
direct screening is appropriate
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Colon screening with more direct test (i.e. colonoscopy)
Start 5-10 years earlier than onset in the family
Sporadic Breast Cancer
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All women have a 1 in 9 (11%) lifetime
chance of developing breast cancer
 usually over 65 years-of-age
Most women over-estimate their risk for
breast cancer and genetic testing is not
beneficial or appropriate for most women
Hereditary
Breast/Ovarian Cancer
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Family History
 How closely related - 1st or 2nd degree relatives
Early ages of onset
 Average age of onset ~39-44years
More than one primary cancer
Ancestry (Icelandic, Ashkenazi Jewish)
Laterality (one side or both sides)
Male breast cancer
Breast Cancer Genes
(BRCA1 and BRCA2)
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Increased Predisposition but not a diagnosis
If BRCA mutation found:
 Genetic testing is available for family
members
If no BRCA mutation found:
 No genetic test available for family
members
If ‘Positive’ for BRCA Mutation
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Additional Options to consider:
 Increased screening
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Lifestyle changes ?
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Clinical breast exams 2 times a year
MRI
Mammograms start 5-10 years earlier than onset in family
Quit smoking
Healthy eating and exercise?
Medical prevention
Prophylactic surgery
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Mastectomy
Oophorectomy
Breast Cancer Genes
Contribution to
Hereditary Breast
Cancer
Gene
BRCA1 (breast, ovarian, prostate)
20%–40%
BRCA2
10%–30%
TP53
(male/female breast, ovarian)
(breast, brain, sarcoma, leukemia, adrenal) <1%
PTEN (breast, thyroid, oral, intestinal)
<1%
<1%
ATM (breast, ionizing radiation sensitivity)
Undiscovered genes
30%–70%
Hereditary Diffuse Gastric Cancer
(HDGC)
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5%-10% of all gastric (stomach) cancers are familial
Gastric cancer seen in several other cancer
syndromes (i.e. HNPCC)
Diffuse - Different pathology (not a tumour mass)
Stomach wall – rubbery, hard, thickened
Average age onset – 38 years
Also see:
 Lobular breast cancer
 Colon cancer
CDH1 gene
Tools for Genetic Assessment
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Family history best predictor
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Maternal & paternal history
 How closely related
Specific types and specific patterns
Clinical and pathology information
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Tumour pathology
 Breast cancer - lobular or infiltrating ductal
 Colon cancer – many polyps or a few polyps
Confirming the diagnosis
 Was it ovarian cancer or cervical cancer?
Multiple Endocrine Neoplasia
(MEN)
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Multiple endocrine neoplasia type 1 (MEN1)
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Pituitary, pancreas, parathyroid tumors
MEN1 gene (chromosome 11)
Multiple endocrine neoplasia type 2 (MEN2)
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Medullary thyroid cancer (~75% sporadic)
Adrenal gland tumours (pheochromocytoma)
Parathyroid disease
RET gene (chromosome 10)
Genetic Counselling…..
What to Expect
Before an appointment:
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Your homework:
 Family History Questionnaire
 Medical records
Our homework:
 Family specific genetic assessment
 Select specific genetic test – if available
Not Always An Obvious PatternNeed the Full (Family) Picture
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Li-Fraumeni syndrome
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Breast cancer
Other cancers in the family
 Bone cancer (Osteosarcoma)
 Soft tissue cancers (Sarcoma)
 Leukemia
Von Hippel Lindau syndrome
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Benign tumours of brain/spine (Hemangioblastoma)
Kidney cancer (renal cell)
Adrenal glands
Genetic Testing Limitations
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Not a ‘yes’ or ‘no’ answer
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Not 100% detection rate
Technical limitations? Other genes to be discovered?
Interpretation of result is unclear
Not all at-risk families are able to be tested
Dx 35
D 43 yr
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1st need to test an appropriate, living affected individual
Based on referral criteria for BRCA testing:
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~ 10% of individuals tested have mutation found
~90% results - ‘no mutation found’
Some Benefits of Genetic Testing
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Identifies high-risk individuals
May help in decision-making
(medical/lifestyle)
Screening and prevention strategies
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May explain cancer pattern if mutation found
May have positive impact family relationships
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May relieve anxiety
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Some Reasons Not to Have
Genetic Testing
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You “wouldn’t do anything different”
Genetic testing does not detect all
mutations
Despite screening options, the cancer risk
not zero
Privacy, insurance or employment concerns?
May increase fear/anxiety – open a
Pandora’s Box
May negatively impact family relationships
Guilt of ‘passing it on’
Review –The Clues That
Cancer Might be Inherited?
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Many individuals in a family
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Affected over many generations
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Three generation family history
Early ages of onset
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On the same side of the family
Often before age 50
Specific patterns and related types
of cancer
Review –What’s Right for You?
Assessment
Family Hx
Genetic Risk
Intervention
Average
(1 in 9)
Sporadic
Standard screening and
prevention recommendations
Moderate
(Familial)
Personalized screening and
prevention recommendations
High
(Hereditary)
Referral for Genetic Evaluation
with personalized screening and
prevention recommendations
Some Things to Remember
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Everyone has 6-12 genes that don’t work
properly – most not a health concern
The chance of developing cancer is never
100% and it is never 0%
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Family history is important
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But Family is more important!!
Thank You!
Patricia Steele
Maritime Medical Genetics
IWK Health Centre
Halifax, NS
902-470-8754