Kristen Rasmussen, MS CGC

1. Heirlooms, Hope Chests,
and Genes…
What did you inherit?
Kristen Rasmussen, MS CGC

2. Your family history
 The cheapest genetic test that exists

3. What to ask about your family
history?
 How old now or when
died?
 What diagnosis (this can
be tricky!)
 What age when
diagnosed?
 With cancer – where did
the cancer START? Did
they get cancer more
than once?

4. What might you find?
 Cancer
 Heart disease
 Diabetes
 Alzheimer’s disease
 Lung disease (COPD, emphysema)

5. What can you do about it?
 Knowing your family history can help you know what you
might be at risk for!
 Help guide screening
 Help instigate change
 Ultimate goal to prevent history “repeating itself”!

6. Genetic or and Environmental
Diabetes
Hypertension
Coronary artery disease
Osteoporosis
Huntington scurvy
Most cancers
AAT deficiency alcoholism
Genetic Environmental
galactosemia Cleft lip/palate Fetal alcohol
syndrome
Spina bifida thalidomide
Down syndrome
Heart defects
Cystic Fibrosis
Clubfoot

7. Most complex diseases have
multiple causes
Some genetic
(the ice cubes)
Some environmental
(the water)

8. Some conditions are more
STRONGLY genetic
 Some conditions can be caused by single genes
 When this is the case, there can be up to a 50% risk to
family members

9. Quick genetics lesson!

10. Chromosome pairs

11. 1st 2nd 3rd
degree degree degree
relatives relatives relatives
Great
Grandparents
Grandparents
Great Aunts
and Uncles
Parents
Aunts
1st cousins
Uncles
You
Nieces Great Nieces
Siblings
Nephews and Nephews
Great
Children Grandchildren
Grandchildren

12. What if your family history
reveals Cancer?
 1 in 3 people get cancer in their lifetime
 Most cancer is not strictly inherited
 2nd leading cause of death in the US
 1 in 4 deaths

14. Breast cancer Risk
Average woman 1 in 12
First degree relative 1 in 8
diagnosed >55
First degree relative 1 in 6
diagnosed <55
First degree relative 1 in 3
diagnosed <45
First degree relative with 1 in 2
bilateral breast cancer
Harper, Peter S. Practical Genetic Counselling, Fifth Edition. Reed
educational and professional publishing 1998.

15. Hereditary Breast and Ovarian
Cancer
 Approximately 5% of all breast cancers
 Up to 87% risk of breast cancer by age 70
 44% risk of ovarian cancer by age 70
 Red flags
 Young age of diagnosis (under age 50)
 Bilateral breast cancer
 Breast and Ovarian in a single individual
 Male breast cancer

16. What can I do differently?
 Be diligent about screening
 Talk to your doctor about options
 GAIL model
 Uses personal history, family history to calculate risk for breast
cancer
 If risk is high enough, can help to determine MRI, preventative
medication eligability
 Change risk factors that can be changed
 Reduce alcohol consumption
 Avoid hormone replacement therapy
 Maintain healthy body weight
 Exercise regularly

17. Colon cancer Risk
Average individual 1 in 50
One first degree relative 1 in 17
One first degree and one 1 in 12
second degree relative
One first degree relative <45 1 in 10
Two first degree relatives 1 in 6
Houlston R.S. et al. (1990) Screening and genetic counselling for
relatives of patients with colorectal cancer in a family cancer clinic.
Br.Med. J. 301. 366-368.

18. Lynch syndrome
 Approximately 5% of all colon cancer diagnoses
 Up to:
 82% risk for colon cancer
 71% risk for endometrial cancer
 12% risk for ovarian cancer
 13% risk for stomach cancer
 Red flags
 Young age of diagnoses (under age 50)
 More than one individual with Lynch-related cancer
 Two Lynch related cancers in same individual

19. What can I do differently?
 Increase screening!
 Colon cancer is one of the few cancers that can be
PREVENTED by screening
 Those with a first degree relative should be getting
colonoscopies at least every 5 years (annually for those
with Lynch syndrome)
 May need to start screening younger
 Again, change risk factors that can be changed
 Quit smoking
 Reduce alcohol consumption
 Lose weight
 Get active!

21. What if your family history
reveals Heart disease?
 1 in every 4 deaths in the US is due to heart disease*
 High blood pressure, high LDL cholesterol, and smoking
are the three biggest risk factors for heart disease*
 ½ of Americans have at least one of the above risk factors*
* CDC website http://www.cdc.gov/heartdisease/facts.htm

22. Death due to Woman age 35- Man age 35-55
Heart attack 55
No close family 1 in 90 1 in 60
member
Male 1st degree 1 in 36 1 in 12
relative
Female 1st degree 1 in 12 1 in 10
relative
Harper, Peter S. Practical Genetic Counselling, Fifth Edition. Reed educational
and professional publishing 1998.

23. Cardiomyopathies
Usually genetic; 55-70% have 20-50% genetic; genetic
identifiable mutations testing not as good
 Dilated
 Hypertrophic

24. Familial Thoracic Aortic Aneurysm
Dissections (TAAD)
 Widening of the blood vessel leading away from the heart
(the aorta)
 If ruptures, can cause sudden death
 Associated with some genetic syndromes such as Marfan
syndrome
 Can also be isolated though
 Genetic testing available, but many
families have an undetectable mutation

25. Familial Hypercholesterolemia
 Very high LDL (bad) cholesterol levels, from birth
 1 in 500 people have it
 1 in 1,000,000 have a severe form (double dose,
inherited from both parents)
* Figure from “Familial Hypercholesterolemia, An educational booklet for patients
with familial hypercholesterolemia” by Dr Leiv Ose

26. Heart history red flags
 Sudden cardiac death, unexplained death at a young
age, or death by an unexplained accident or drowning.
 Heart attack prior to age 50.
 Heart failure at a young age (under 50). Signs of heart
failure include shortness of breath, fatigue, weakness,
difficulty with exercise and "asthma" that doesn't
improve with an inhaler.
 Palpitations or an abnormal heart rhythm at a young
age.
 Fainting, black-outs, or seizures that couldn't be treated
with typical seizure medications.
 More than one relative with the same type of heart
disease.

27. What can I do differently?
 Talk with your doctor about screening and preventative
options (differs depending upon the form of heart disease in
your family)
 Periodic echocardiograms for those with a family history of
cardiomyopathy or Familial Thoracic Aortic Aneurysm
Dissections (TAAD)
 Medications/implantable devices for those found to have early
stages of cardiomyopathy/TAAD
 Early cholesterol screening (in early childhood) for families with
familial hypercholesterolemia.
 Medications for those with elevated cholesterol levels
 Change environmental factors that can be changed (again,
differs depending upon form of heart disease)
 Manage cholesterol, blood pressure, diet, exercise

28. What if your family history
reveals Diabetes?
 1 in 12 Americans have diabetes*
 1 in 4 over the age of 65*
 If current trends continue, 1 in 3 by 2050*
 Vast majority (95%) are type II diabetes
 Age, obesity, family history, a history of gestational
diabetes, inactivity, and race/ethnicity are major risk
factors
*CDC website http://www.cdc.gov/features/diabetesfactsheet/

29. Diabetes Type I Type II
General Population 1 in 300 1 in 100 to 1 in 12
With affected 1 in 14 1 in 10
silbing
With affected 1 in 25 1 in 10
parent
With two affected 1 in 2
parents

30. MODY (Maturity Onset Diabetes
of the Young)
 1-5% of the cases of diabetes in the US
 Caused by a single gene alteration in a gene that affects
the pancreas’ ability to produce insulin
 Affected individuals often thin, with no risk factors for
diabetes
 Can present in childhood, but may remain undetected
until adulthood
 Often can be managed with medications, rather than
insulin
 If untreated, can cause damage to eyes, kidneys,
nerves, blood vessels

31. What can I do differently?
 Talk to your doctor
 More frequent/earlier screening
 Change risk factors that can be changed
 Exercise /diet
 Get blood pressure/cholesterol under control
 Weight loss
 Losing 5-7% of body weight and getting 150 minutes of
moderate exercise/week can reduce risk of diabetes by 60% in
high risk individuals*
* CDC website http://www.cdc.gov/features/diabetesfactsheet/

32. What if your family history
reveals Alzheimer’s disease?
Alzheimer’s disease Lifetime risk
General population 10.5%
Affected first degree relative 20-25%
 Additional affected relatives probably increases this risk
 One study showed that for people with an affected parent
and sibling (prior to age 70), the risk to develop AD was 35-
45%
 If both parents affected, also likely increased risk

33. ApoE and the link to Alzheimer’s
disease
 Apolipoprotein E is a protein that is important in carrying
cholesterol and fat in the bloodstream
 Several varieties of this gene.
 ApoE2
 ApoE3 (most common)
 ApoE4
 The ApoE4 version of the gene has been linked to an
increased risk of Alzheimer’s disease
 Women with e4/e4 genotype have a 45% risk of developing
AD by the age of 73
 Men with e4/e4 have a 25% risk
 ApoE2 may have a protective effect

34. Individuals
with AD and
Normal All Individuals Positive
APOE
Controls with AD Family
Genotype
(n=304) (n=233) History of
Dementia 1
(n=85)
e2/e2 1.3% 0% 0%
e2/e3 12.5% 3.4% 3.5%
e2/e4 4.9% 4.3% 8.2%
e3/e3 59.9% 38.2% 23.5%
e3/e4 20.7% 41.2% 45.9%
e4/e4 0.7% 12.9% 18.8%
Modified from Jarvik et al [1996]

35. What can you do differently?
 ApoE is NOT typically recommended as a predictive test
 Even those with e4/e4 have a greater chance of NOT
developing Alzheimer disease
 No effective prevention
 If concerned about risk, could consider a baseline
neuropsych evaluation
 Provides a baseline study to compare to in the future,
should concerns arise
 No preventative medications, but medications approved
to treat early stages of AD
 Clinical trials (www.clinicaltrials.gov)

36. Early onset Alzheimer’s disease
 Under age 60 (though not a strict cut off)
 Accounts for less than 5% of people with Alzheimer’s
disease
 Strongly genetic PSEN1 (30-70%)
PSEN2 (less than 5%)
APP (10-15%)
Other genes, currently
unknown

37. What if your family history
reveals Lung disease
 Rates in women have increased over the past 20 years
 Smoking increases risk of Chronic Obstructive Pulmonary
Disease (COPD) by 12-13 times
 75% of COPD attributed to smoking

38. Alpha 1 antitrypsin deficiency
 1 in 5000 individuals
 Lung disease after age 20
 Smoking significantly increases the risk for lung disease and the age of
onset
 Liver disease from infancy to over age 50
 Extremely common to be a carrier (1 in 15 – 1 in 20)
 Very common among Scandinavians
 Carriers have a slight increase in risk for lung/liver disease

39. Alpha-1-antitrypsin Red flags
 Early onset of emphysema (age 45 years or less)
 COPD – emphysema or chronic bronchitis
 Family history of emphysema/COPD, liver disease
 Asthma with minimal response to medication,
inhalers
 Liver disease with unknown cause
 http://www.alpha1health.com/patients-and-
families/testing-for-alpha-1/alphatest-kit.html

40. What can you do differently?
 Avoid environmental exposures!
 Smoking / 2nd hand smoke
 Dust/fumes/occupational exposures (wear a mask)
 Avoid other risk factors for liver disease for those with
Alpha-1-antitrypsin deficiency
 Talk with your doctor
 Screening available, recommended for those who smoke

41. How to record your own family
history
 Ask questions!
 Ask not just “who”, but also how old?
 Ask about illnesses, and what age they were
when diagnosed
 For cancers, ask where did the cancer
START?
 Write down the answers
 Update regularly
 Share your project with your family – they
will be more likely to help and become
interested!
 https://familyhistory.hhs.gov/fhh-
web/home.action

42. How can I get records on a
deceased family member?
 Find out where they were seen for
their care
 Next of Kin has right to sign for
medical records to be released.
 Spouse
 Children / Parents
 Siblings / Grandchildren
 Uncles, Aunts / Neices, Nephews
/ Great Grandchildren
 Sign a release of Information form
 Free if records released to a
medical provider
 Can be cost if released directly to
you

43. DNA banking
 A way to save blood/DNA for the future
 Costs around $100 (not covered by insurance)
 Available at a number of private laboratories

44. November is family health history
month!

45. Questions?