Heirlooms, Hope Chests, and Genes… What did you inherit?

Kristen Rasmussen, MS CGC

Your family history

The cheapest genetic test that exists

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?

What might you find?

Cancer

Heart disease

Diabetes

Alzheimer’s disease

Lung disease (COPD, emphysema)

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”!

Genetic or and Environmental

Genetic Environmental

Down syndrome

Cystic Fibrosis

thalidomide

Cleft lip/palate

Spina bifida

Heart defects

Clubfoot

Diabetes

Hypertension

Coronary artery disease

Osteoporosis

Most cancers AAT deficiency

scurvy Huntington

alcoholism

Fetal alcohol

syndrome galactosemia

Most complex diseases have multiple causes

Some genetic

(the ice cubes)

Some environmental

(the water)

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

Quick genetics lesson!

Chromosome pairs

3rd degree

relatives

2nd degree

relatives

1st degree

relatives

You

Parents

Grandparents

Great Grandparents

Great Aunts and Uncles

Aunts

Uncles 1st cousins

Siblings Nieces

Nephews

Great Nieces and Nephews

Children Grandchildren Great

Grandchildren

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

Breast cancer Risk

Average woman 1 in 12

First degree relative diagnosed >55

1 in 8

First degree relative diagnosed <55

1 in 6

First degree relative diagnosed <45

1 in 3

First degree relative with bilateral breast cancer

1 in 2

Harper, Peter S. Practical Genetic Counselling, Fifth Edition. Reed educational and professional publishing 1998.

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

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

Colon cancer Risk

Average individual 1 in 50

One first degree relative 1 in 17

One first degree and one second degree relative

1 in 12

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.

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

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!

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

Death due to Heart attack

Woman age 35-55

Man age 35-55

No close family member

1 in 90 1 in 60

Male 1st degree relative

1 in 36 1 in 12

Female 1st degree relative

1 in 12 1 in 10

Harper, Peter S. Practical Genetic Counselling, Fifth Edition. Reed educational and professional publishing 1998.

Cardiomyopathies

Dilated

Hypertrophic

20-50% genetic; genetic testing not as good

Usually genetic; 55-70% have identifiable mutations

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

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

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.

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

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/

Diabetes Type I Type II

General Population 1 in 300 1 in 100 to 1 in 12

With affected silbing

1 in 14 1 in 10

With affected parent

1 in 25 1 in 10

With two affected parents

1 in 2

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

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/

What if your family history reveals Alzheimer’s disease?

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

Alzheimer’s disease Lifetime risk

General population 10.5%

Affected first degree relative 20-25%

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

APOE Genotype

Normal Controls (n=304)

All Individuals with AD (n=233)

Individuals with AD and Positive Family 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]

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)

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, currentlyunknown

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

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

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

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

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

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

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

November is family health history month!

Questions?