Genetics: For this Generation and the Next

Andrea Forman, MS, LCGC Fox Chase Cancer Center

Risk Assessment ProgramDepartment of Clinical Genetics

Common Diseases

• Cancer

• Heart disease

• Diabetes

• Hypertension

• Stroke

• Alzheimer's

• Arthritis

• Osteoporosis

Common Risk Factors

• Age

• Family history

• Ethnicity

• Lifestyle

• Diet

• Alcohol

• Smoking

Top 5 Reasons to Know Your Family History

5. Family recipes should be kept secret — family medical history should not.

4. Knowing your risk might save your life.

3. It’s free and you don’t have to leave home.

2. It’s a priceless gift to leave to your children.

1. Because every family has a story, but not every family has YOUR story.

https://www.yahoo.com/health/10-reasons-you-should-dig-into-your-family-medical-118232923367.html

Genetic information is key

What is a Gene?

DAD MOM

Cancer and Genetics

Fortune Cookie Tip #1

Family history was the first genetic test

Clues:Genetic Risk for Cancer

• YOUNG– Breast <45, Colon <50

• RARE– Examples include Ovarian, Male Breast, Pancreatic

• MULTIPLE– Two or more different cancers in the same person

• FAMILY– Two or more family members with the same or related types

of cancer. • Breast/Ovary. Breast/Thyroid/Uterine. Breast/Sarcoma/Brain

Colon, 72

Sporadic Family History

Risk for cancer is AVERAGE

Familial Family History

Prostate, 75

Lung, 65coal miner

Stomach, 55H. pylori

Liver, 50alcohol abuse

CervixHPV, smoker

Lung, 58smokerBasal Cell

sun exposure

Risk for cancer is MODERATE

Hereditary Family History

Breast, 55

Ovarian, 44

Breast, 34

Prostate,59

Breast, 50

Risk for cancer is HIGH

Fortune Cookie Tip #2

Don’t forget to look at both sides of the

family!

Why would I want to know?

• Possible risk of another, new cancer

• Risks to your children

• Risks to other family members

• Screening and prevention are often available and may save a life

Family history of breast cancer? Who is the best person to test?

New yellow apple

Red apple tree growing one yellow apple

Courtesy of Kallie Weinan, MS, CGC

Red apple tree growing red apples

Fortune Cookie Tip #3

When searching for something rare, start the search with the

most likely target.

BRCA1 +BRCA1 -

Does not want testing

BRCA1 +BRCA1 -

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Breast Ovary Prostate (male) Breast (male) Pancreas

Gen. Population BRCA Carrier

Cancer Risks with HBOC

What Can You Do?

Increased screening

• Start Earlier– 25yo for breast screening

• More Often– Alternating imaging every

6 months

• More Aggressive– Mammogram

+

Breast MRI

Prevention

• Medication– Tamoxifen (breast

cancer risk)– Birth control pills (ovarian

cancer risk)

• Surgery– Risk reducing mastectomy– Salpingo-oophorectomy

(removal of ovaries and fallopian tubes)

Guess what?

You won’t be seeing many tests

for just BRCA1/2 anymore

Multi-Gene (NGS) Panels

• Genetic tests to look at dozens of genes related to cancer

• Similar cost and turn around time as gene specific testing

• Higher risk of uncertain results

NGS Panels- Breast

Walsh et. al. 2013 (ASHG Platform Presentation)

•800 families with negative BRCA1/2 testing– 206 tested positive with NGS BROCA panel (26%)

•Of the 26% with a new positive results–39% (80/206) had BRCA1/2 mutations–37% carried mutations in CHEK2, PALB2, or TP53–20% carried mutations in 10 less characterized genes

Ms. Smith

• 46 year old woman with a newly diagnosed left breast cancer– ER/PR+ invasive ductal carcinoma

• Referred to Risk Assessment as patient wants risk estimate to help her make a decision about bilateral mastectomy

NGS Test Result

Positive for a gene mutation

• CHEK2

Variants of Uncertain Significance

• BRCA 2

• STK11

Fortune Cookie Tip #4

Sometimes, in our quest for answers, we end up with

more questions

Moderate Risk Genes

• Cancer risks may not be very high– How high does risk need to be before we

pursue surgery or medications?

• Cancer risks may be unclear– How do we make medical decisions when we

don’t know the risks?

• We’re still learning– The recommendations you get today may be

different in 5 years

NGS Test Result

Positive for a gene mutation

• CHEK2

Variants of Uncertain Significance

• BRCA 2

• STK11

N=398

Rates of Uncertain Variants

Eggington et. al. Current Variant of Uncertain Significance Rates in BRCA1/2 and Lynch Syndrome Testing (MLH1, MSH2, MSH6, PMS2, EPCAM), March 2012, ACMG Poster Presentation.

Isn’t it just a blood test?

• Positive results with limited information

• Inconclusive results

• Results that don’t “fit”

• Worry/anxiety

Consider This…

• Unclear results

• Limited data• Limited

usefulness • Changes in

technology

BENEFITS

• Anxiety/ distress

• Privacy• Appropriate

follow-up?

• Clarification of risk

• Guidance for medical management

• Information for family

RISKS LIMITATIONS

What can you do?

• Know your family history

• Educate your family about its history

• Talk to your doctor or a genetic counselor

What is a Genetic Counselor?

I am a translator

NSGC: www.nsgc.org

Questions?

Andrea Forman, MS, LCGCGenetic Counselor

Department of Clinical Genetics, Fox Chase Cancer Center

1-877-627-9684

www.fccc.edu/rap

rapinfo@fccc.edu