Call-on Congress 2014 Heather Hampel: Genetics

Genetics: The role of
genetic syndromes in
patients & family members
Heather Hampel, MS, CGC
Professor, Division of Human Genetics
November 5, 2011

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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
Most cancers are not inherited
5-10% hereditary10-15% familial
75-85% sporadic

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Research Institute
Who is at high risk for cancer?
History is the key…

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Research Institute
CLUES:
§  Cancer in 2 or more close relatives
(on same side of family)
§  Early age at diagnosis
§  Bilateral/multiple cancers
§  Multiple rare cancers
§  Multiple primary tumors (breast and ovary;
colon and uterus)
§  Evidence of autosomal dominant transmission

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Research Institute
CAUTION

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Research Institute
Family History can be unreliable
§  Many people do not know the details of their family
history.
§  Specific sites of tumors unknown
§  Ages of onset unknown
§  Historical information needs to be verified in order to
accurately assess risk.
§  Family size is getting smaller – can “hide”
susceptibility
§  Increased use of effective screening/prevention
options (i.e. colonoscopy) can prevent cancers that
would have occurred otherwise

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Research Institute
Initial pedigree After review of records
Stomach
Ca
Prostate
problems
Bone Ca
d. 48
Breast Ca
dx 45
d. 48
Ovarian Ca
dx 43, d. 49
Prostate Ca
dx 50

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Research Institute
Histories are dynamic
§  With the passage of time, additional diagnoses may
have been made.
§  These changes in diagnosis may affect the likelihood
of a hereditary cancer syndrome.

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Research Institute
Initial History 2 years later
Colon Ca, 50
Colon Ca, 50
Endometrial
Ca, 44
Colon polyps, 48

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Research Institute
High Risk Families
§  CRC or EC diagnosed under age 50
§  Patients with 2-3 cases of the same or related
cancers on the same side of the family
§  Patients with multiple primary cancers
§  Certain tumors are enough on their own
§  Sebaceous adenoma / adenocarcinoma of skin
§  Patients with certain pathology findings
§  CRC or EC with abnormal IHC or MSI+ testing

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Research Institute
Patient & Family Implications: Lynch Syndrome
MLH1
PMS2
MSH2 MSH6

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Research Institute
Sporadic Inherited
•  Later age at onset (60s or 70s)
•  Little or no family history of cancer
•  Single or unilateral tumors
• Early age at onset (<50)
• Multiple generations with
cancer
• Clustering of certain cancers
(i.e. breast/ovarian)
Normal gene
Somatic
mutation
Somatic
mutation
Germline
mutation
Somatic
mutation

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Research Institute
Autosomal Dominant Inheritance
Carrier Parent Non-carrier Parent
Aa aa
Aa Aa aa aa
Carrier Carrier Non-carrier Non-carrier
1/2 1/2

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Research Institute
Lynch Syndrome Cancer Risks (to 70)
Cancer Lynch syndrome General Public
Colon cancer 56-85% 5%
Endometrial cancer 35-60% 2%
Gastric cancer 13% 1%
Ovarian cancer 12% 1.5%
Small bowel, bladder,
ureter, renal pelvis, brain
<4% each <1% each

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Research Institute
Lynch syndrome Surveillance Options
Lindor N et al. JAMA 2006;296:1507-17. & Vasen HFA et al. J Med Genet 2007;44:353-62.
Intervention Recommendation
Colonoscopy Every 1-2 y beginning at age 20-25 (MLH1 &
MSH2), or 30 (MSH6 & PMS2)
Endometrial sampling Every 1 y beginning at age 30-35
Transvaginal U/S Every 1 y beginning at age 30-35
Urinalysis with cytology Every 1-2 y beginning at age 30-35
History & Exam w/
review of systems
Every 1 y beginning at age 21

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Research Institute
Moderate Risk Families
§  1-2 cases of a cancer in the family
§  Do not need referral for genetic counseling
§  Do need increased cancer surveillance
§  Generally the first degree relatives of a person with a
cancer are about twice as likely to develop that same
cancer than someone without that family history

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Research Institute

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Research Institute
Familial Colorectal Cancer Risks
Taylor, DP, Gastroenterology 2010;138:877-886.

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Research Institute
Familial Colorectal Cancer Screening
Recommendations
§  FDR diagnosed <50 or 2 FDR dx at any age
§  Colonoscopy every 3-5 years beginning at age 40 (or
10 years before earliest dx of CRC
§  FDR diagnosed >50
§  Colonoscopy every 5 years beginning at age 50 (or
10 years before earliest dx of CRC
§  SDR diagnosed <50
§  Colonoscopy beginning at age 50 repeat depending
on findings
§  Otherwise follow Average Risk recommendations
§  Colonoscopy every 10 years beginning at age 50

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Research Institute
Family Healthlink
§  Interactive web tool that estimates risk by
reviewing patterns of cancer and heart disease
and related conditions in a family
§  10-15 min depending on the size of the family
§  No pedigree to view; no updating
§  Personalized risk assessment (pdf) to share with
healthcare providers
https://familyhealthlink.osumc.edu

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Research Institute
Genetic Counseling

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Research Institute
Genetic Counseling:
Purpose
§  Appreciate the way heredity contributes to
cancer
§  Understand an individual’s risk of
developing cancer
§  Understand the options for dealing with an
increased risk for cancer
§  Choose a course of action for managing
cancer risk that seems personally
appropriate (genetic testing, screening or
long-term follow up)

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Research Institute
Genetic Counseling:
What happens
§  Collection of personal and family history
§  3 generation pedigree
§  Education and risk assessment
§  Options for genetic testing and medical
management
§  Discussion of risks, benefits and limitations
§  Screening/Chemoprevention/Prophylaxis
§  Follow-up
§  Provide psychosocial support
§  Family members

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Research Institute
GINA
§  Prevents health insurers from denying coverage,
adjusting premiums, or otherwise discriminating on the
basis of genetic information.
§  Group and self-insured policies
§  Insurers may not request that an individual undergo a
genetic test.
§  Employers cannot use genetic information to make
hiring, firing, compensation, or promotion decisions.
§  Sharply limits a health insurer's or employer's right to
request, require, or purchase someone's genetic
information.

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Research Institute
Resources
§  Heather Hampel
§  614-293-7240
§  Heather.Hampel@osumc.edu
§  Family HealthLink
§  https://
familyhealthlink.osumc.edu
§  Free, on-line tool that
assesses family history of
cancer and cardiovascular
disease

Call-on Congress 2014 Heather Hampel: Genetics

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