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% hereditary 10-15% familial

75-85% sporadic

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

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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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CAUTION

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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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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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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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Initial History 2 years later

Colon Ca, 50 Colon Ca, 50

Endometrial Ca, 44

Colon polyps, 48

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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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Patient & Family Implications: Lynch Syndrome

MLH1

PMS2

MSH2 MSH6

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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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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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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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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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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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Familial Colorectal Cancer Risks

Taylor, DP, Gastroenterology 2010;138:877-886.

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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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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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Genetic Counseling

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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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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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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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Resources §  Heather Hampel

§  614-293-7240 §  [email protected]

§  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

Health & Medicine

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