1. 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.

2. Cancer Care Nova Scotia
Hereditary Cancer
Cancer Answers
Cancer Care Nova Scotia
May 20th, 2008
Patricia Steele, MSc, CCGC, CGC
Genetic Counsellor
Maritime Medical Genetics Services
IWK Health Centre
and Genetic Testing

3. 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

4. Cell Growth and Development
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

5. Cancer – Abnormal Cell Growth
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

6. Cancer: When is it Inherited?
~ 85% Sporadic (by chance)
~ 10% Familial
~ 5% Hereditary

7. Sporadic Cancer History
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

8. Familial Cancer History
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

9. Hereditary Cancer History
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

10. Quick Genetic Review

11. The genome is like an encyclopedia...

12. A Gene is Like A Recipe for Making A Specific Protein

13. Everyone Has Changes In Their DNA
Some changes have no medical effect
A harmful change in the DNA is called a ‘mutation’
Mutations prevent the gene from working properly 

14. 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

15. 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)

16. Some Genes Repair DNA Errors (The DNA Mechanics)

17. Many Cellular Changes Involved

18. Inherited or Acquired Gene Mutations

19. Dominant Inheritance does not cause cancer
increases risk for developing cancer

20. Inherited Cancer Syndromes
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

21. Inherited Colon Cancer
Hereditary nonpolyposis colon cancer (HNPCC)
Familial adenomatous polyposis (FAP)
~ 1% of hereditary colon cancer
Attenuated FAP (later age onset)
MYH Associated Polyposis (MAP)
~ 1% of hereditary colon cancers

22. Hereditary Nonpolyposis Colon Cancer (HNPCC)
Small number of polyps
Many DNA repair genes involved
Also called Lynch syndrome
Type 1– Colon cancer
Type 2-
Colon
Uterine, breast, pancreas, ovarian, bile duct

23. Familial Adenomatous Polyposis (FAP)
~1% hereditary colon cancers
Hundreds of polyps
Onset of polyps - teen years
Start screening no later than age 10
Average age of cancer diagnosis – age 38
If no treatment – v. high likelihood of cancer
Attenuated FAP (AFAP)
multiple polyps
Later age onset of colon cancer (<60 years)
APC gene - good detection rate (~80-90%)

24. MYH-Associated Polyposis (MAP)
Families with multiple polyps (like AFAP)
But do not identify APC gene mutation
new gene found – MYH
~10% of AFAP-like families
Screening beginning in 20’s
Recessive inheritance
inherit 2 non-working genes
See in siblings

25. Routine Screening ? Increased Screening?
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
Colon screening after age 50
Fecal Occult Blood Test (FOBT)
If family history or inherited predisposition then more direct screening is appropriate
Colon screening with more direct test (i.e. colonoscopy)
Start 5-10 years earlier than onset in the family

26. Sporadic Breast Cancer
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

27. Hereditary Breast/Ovarian Cancer
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

28. Breast Cancer Genes (BRCA1 and BRCA2)
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

29. If ‘Positive’ for BRCA Mutation
Additional Options to consider:
Increased screening
Clinical breast exams 2 times a year
MRI
Mammograms start 5-10 years earlier than onset in family
Lifestyle changes ?
Quit smoking
Healthy eating and exercise?
Medical prevention
Prophylactic surgery
Mastectomy
Oophorectomy

30. Contribution to Hereditary Breast Cancer
Breast Cancer Genes
Contribution to Hereditary Breast Cancer
20%–40%
10%–30%
<1%
30%–70%
Gene
BRCA1 (breast, ovarian, prostate)
BRCA2 (male/female breast, ovarian)
TP53 (breast, brain, sarcoma, leukemia, adrenal)
PTEN (breast, thyroid, oral, intestinal)
ATM (breast, ionizing radiation sensitivity) Undiscovered genes

31. Hereditary Diffuse Gastric Cancer (HDGC)
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

33. Tools for Genetic Assessment
Family history best predictor
Maternal & paternal history
How closely related
Specific types and specific patterns
Clinical and pathology information
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?

34. Multiple Endocrine Neoplasia (MEN)
Multiple endocrine neoplasia type 1 (MEN1)
Pituitary, pancreas, parathyroid tumors
MEN1 gene (chromosome 11)
Multiple endocrine neoplasia type 2 (MEN2)
Medullary thyroid cancer (~75% sporadic)
Adrenal gland tumours (pheochromocytoma)
Parathyroid disease
RET gene (chromosome 10)

35. Genetic Counselling….. What to Expect
Before an appointment:
Your homework:
Family History Questionnaire
Medical records
Our homework:
Family specific genetic assessment
Select specific genetic test – if available

36. Not Always An Obvious Pattern- Need the Full (Family) Picture
Li-Fraumeni syndrome
Breast cancer
Other cancers in the family
Bone cancer (Osteosarcoma)
Soft tissue cancers (Sarcoma)
Leukemia
Von Hippel Lindau syndrome
Benign tumours of brain/spine (Hemangioblastoma)
Kidney cancer (renal cell)
Adrenal glands

37. Genetic Testing Limitations
Not a ‘yes’ or ‘no’ answer
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
1st need to test an appropriate, living affected individual
Based on referral criteria for BRCA testing:
~ 10% of individuals tested have mutation found
~90% results - ‘no mutation found’
Dx 35
D 43 yr

38. Some Benefits of Genetic Testing
Identifies high-risk individuals
May help in decision-making (medical/lifestyle)
Screening and prevention strategies
May explain cancer pattern if mutation found
May have positive impact family relationships
May relieve anxiety

39. Some Reasons Not to Have Genetic Testing
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’

40. Review –The Clues That Cancer Might be Inherited?
Many individuals in a family
On the same side of the family
Affected over many generations
Three generation family history
Early ages of onset
Often before age 50
Specific patterns and related types of cancer

41. Review –What’s Right for You?
Assessment
Genetic Risk
Intervention
Standard screening and prevention recommendations
Average
(1 in 9)
Sporadic
Personalized screening and prevention recommendations
Moderate
(Familial)
Family Hx
High
(Hereditary)
Referral for Genetic Evaluation
with personalized screening and prevention recommendations

42. Some Things to Remember
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%
Family history is important
But Family is more important!!

43. Maritime Medical Genetics
Thank You!
Patricia Steele
Maritime Medical Genetics
IWK Health Centre
Halifax, NS