family first: what you need to know about family history, genetic testing, and colorectal cancer
DESCRIPTION
Have you and your family talked about the importance of knowing your family's medical history? Did you know that 3% of all colorectal cancers are due to a syndrome called Lynch syndrome? Having Lynch syndrome puts you at an 80% increased risk of developing colorectal cancer. This webinar will focus more about Lynch Syndrome and other inherited syndromes as they relate to colorectal cancer. Heather Hampel, a genetics counselor from Ohio State University will discuss the importance of knowing your family history. She'll talk about when, how and where to find a genetics counselor, and what is it you should discuss with them.TRANSCRIPT
Welcome to Fight Colorectal Cancer’s Webinar
Family First: What you need to know about genetic testing,
family history& colorectal cancer
Our webinar will begin shortly.
Today’s Webinar:1. Today’s Speaker: Heather Hampel, MS, CGC
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Speaker
Heather Hampel, MS, CGCOhio State University
Comprehensive Cancer CenterTwitter: @hhampel1
Family First: What you need to know about genetic testing, family history & colorectal cancer
Heather Hampel, MS, CGCProfessor, 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Who is at high risk for cancer?History is the key…
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Family History
An important first step in risk assessment for genetic diseases and other hereditary health conditions
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Genetic Family History – My Family Health Portrait
• “The family tree has become the most important genetic test of all…”
• To help focus attention on the importance of family health history, U.S. Surgeon General in cooperation with other agencies within the U.S. Department of Health and Human Services (HHS) has launched a national public health campaign, called the U.S. Surgeon General's Family History Initiative, to encourage all American families to learn more about
their family health history. http://www.hhs.gov/familyhistory/
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
My Family Health Portrait• Americans know that family history is
important to health. A recent survey found that 96 percent of Americans believe that knowing their family history is important. Yet, the same survey found that only one-third of Americans have ever tried to gather and write down their family's health history. http://www.hhs.gov/familyhistory/
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
My Family Health Portrait• Because family health history is such a
powerful screening tool, the Surgeon General has created a new computerized tool to help make it fun and easy for anyone to create a sophisticated portrait of their family's health. http://www.hhs.gov/familyhistory/
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
National Family History Day• Thanksgiving is an annual National
Family History Day. Thanksgiving is the traditional start of the holiday season for most Americans.
• Whenever families gather, the Surgeon General encourages them to talk about, and to write down, the health problems that seem to run in their family. Learning about their family's health history may help ensure a longer future together.
• http://www.hhs.gov/familyhistory/
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Family history is a risk factor for diseases throughout all stages of
life
infantschildren
adolescents
adults older adults
birth defectsblood
disorders
Alzheimer’s disease
osteoporosis
cancerheart
disease
diabetesdepressio
n
asthma
autism
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Taking a Family History
Obtain at least a three-generation pedigree
Ask about all individuals in the family and record: Age at any diagnosis, age at and
cause of death Any corrective surgeries Associated congenital abnormalities
Record ethnicity and religious background Some cancer syndromes are more common
in individuals from certain ethnic groups
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Three-Generation Pedigree
Colon cancerdx 4062
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German/Polish English/Irish
Endometrial Cancerdx 49d. 72
d. 80
67 5565 Diabetes, dx 45 59
52
30
d. 70 d. 85
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Family History Questionnaires
Name
Davis, John
Jones, Mary
Date of Birth
2/1/40
4/9/42
Age at dx/ Type of Cancer
CRC dx 48
Endometrial dx 52
Date of
Death
4/3/87
N/A
Hospital
U. Minn.
Franklin Medical center
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Information to Obtain About Affected Relatives
Current age Age at and date of diagnosis/death Type and number of colon polyps Type and location of cancer Primary cancer location vs. metastatic
cancer site Hospital where treated Environmental exposures (eg, sun)
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Information to Obtain About Unaffected Relatives
Current age
Health status and history of significant illnesses
Presence of other physical findings associated with syndromes
If deceased, cause of and age at death
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
“Female” cancer
Ask about the presenting features Detected by Pap smear – likely cervical cancer Diagnosed due to heavy bleeding – likely
uterine/endometrial cancer Bloated (looked 6 months pregnant) – likely ovarian
cancer
Ask about the treatment Hysterectomy but ovaries left behind – probably not
ovarian cancer No chemotherapy – probably NOT ovarian cancer LEEP procedure or colposcopy – probably cervical
dysplasia or cancer
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Unknown type of cancer
Request copies of medical records (pathology reports are the key) from the hospital where the relative was treated If a family member makes the request, there will be a
charge for the records If you physician or genetic counselor makes the
request, there will not be a charge for the records
Request death certificates Can be obtained from the state department of health
relatively inexpensively Can be obtained at www,vitalchek.com from any state
– arrive quickly, slightly more expensive
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
High Risk Clues: Cancer in 2 or more close relatives
(on same side of family)
Multiple generations affected
Early age at diagnosis
Multiple rare cancers (sebaceous skin cancer)
Multiple primary tumors (colon and uterus; more than one colon cancer)
Multiple colon polyps (>10) Patients with certain pathology findings
Abnormal IHC or MSI+ testing
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
CAUTION
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Initial pedigree After review of records
Stomach Ca
Prostateproblems
Bone Cad. 48
Breast Cadx 45d. 48
Ovarian Cadx 43, d. 49
Prostate Cadx 50
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Initial History 2 years later
Colon Ca, 50Colon Ca, 50
Endometrial Ca, 44
Colon polyps, 48
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Flowchart for Hereditary Colon Cancer Differential Diagnosis
Presence of >10 polyps
Type of polyps
Lynch syndromeFamilial Colorectal Cancer
syndrome type XMUTYH-Associated Polyposis
Peutz-Jeghers syndromeJuvenile Polyposis
Serrated Polyposis syndrome
Familial Adenomatous Polyposis Attenuated FAP
MUTYH-Associated Polyposis
NoYes
AdenomatousHamartomatous
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Hereditary Cancer Syndromes: Lynch Syndrome & FAP
MLH1
PMS2
MSH2 MSH6 APC
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Lynch Syndrome
Early but variable age at CRC diagnosis (~45 years)
Tumor site in proximal colon predominates
Extracolonic cancers: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Amsterdam II criteria
• 3 or more relatives with verified HNPCC-associated cancer in family
• Two or more generations• One case a first-degree relative of the
other two• One CRC dx <50• FAP excluded
Vasen HFA et al. Gastroenterology. 116:1453, 1999
Does not include ovarian, gastric, brain,
biliary tract or pancreatic cancer
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Bethesda Guidelines
Individual with CRC dx <50 Individual with synchronous or metachronous
CRC, or other HNPCC-associated tumors regardless of age
Individual with CRC with MSI-H histology dx <60 Individual with CRC with >1 FDR with an
HNPCC-associated tumor, with one cancer dx <50
Individual with CRC with >2 FDRs or SDRs with an HNPCC-associated tumor, regardless of age
Umar A, et al. JNCI. 2004;96(4):261-268.
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Case 1
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Case 2
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Clinical Features of FAP
Estimated penetrance for adenomas >90%
Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other)
CHRPE may be present
Untreated polyposis leads to 100% risk of cancer
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Attenuated FAP
Later onset (CRC ~age 50) Few colonic adenomas Not associated with CHRPE UGI lesions Associated with mutations at
5' and 3' ends of APC gene
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
MUTYH-Associated Polyposis (MAP) Recessive inheritance – carrier frequency high Biallelic MYH mutations are found in:
96/1457 (6.6%) patients with >100 adenomas 233/3253 (7%) patients with 20-99 adenomas 37/970 (4%) patients with 10-19 adenomas 19/1147 (2%) patients with <10 adenomas
Y165C & G382D common in W.E. Caucasians E466X in Eastern Indian families
Grover S et al. JAMA 2012;308:485-92.
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
MUTYH-Associated Polyposis (MAP)
MYH mutations in CRC dx <50 8/1116 (0.7%) + 12/1238 (1%) + 4/64 (6.3%) +
Heterozygote risk 14/259 heterozygotes had adenomas vs 2/107
controls 2/50 obligate carrier parents had CRC – Expected If there is a cancer risk for heterozygotes – LOW
Wang L et al. Gastroenterology 2004;127:9-16; Croitoru S et al. J Natl Cancer Inst 2004;96:1631-4.Balaguer et al. Clin Gastroenterol Hepatol 2007;5:379-87
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
MAP Management
Colonoscopy every 2-3 y begin at 25-30 if negative for polyps
Once polyps are found, colonoscopy and polypectomy every 1-2 y
Subtotal colectomy or proctocolectomy depending on adenoma density and distribution
Consider UGI endoscopy and side viewing duodenoscopy begin at 30-35 and repeat depending on findings
Annual physical examination
NCCN Guidelines for Colorectal Cancer Screening 2.2014
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Who to test for FAP & MAP? APC testing criteria
Personal history of >10 adenomas Personal history of a desmoid tumor Known APC mutation in family
MUTYH testing criteria Personal history of >10 adenomas Individual meeting SPS criteria with some adenomas Known MUTYH mutations in family
Start testing with affected relative if possible If affected relative is deceased, can test at-risk
relative but negative result is uninformative Can test minors because cancer screening starts in
childhood
NCCN Guidelines for Colorectal Cancer Screening 2.2014
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Familial Colorectal Cancer Risks
Taylor, DP, Gastroenterology 2010;138:877-886.
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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
FDR with advanced adenoma(s) Colonoscopy beginning at age 50 or age of onset repeat
depending on findings Otherwise follow Average Risk recommendations
Colonoscopy every 10 years beginning at age 50
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Genetic Counseling
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Genetic Testing:Purpose
If the exact gene mutation can be identified in a family, it can: Diagnose the family with a specific cancer syndrome Determine for which cancers the family is at risk Determine a cancer surveillance & prevention plan Allow at-risk family members to be tested
inexpensively and reliably Relatives who inherit the mutation need to follow the
increased cancer surveillance & prevention plan Relatives who do NOT inherit the mutation can follow
the American Cancer Society guidelines for cancer screening in the general population 50 colonoscopies versus 3 colonoscopies
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Genetic Testing:What happens
Testing is most accurate when you begin by testing a family member who has had cancer (or polyps) If they test positive, the family has a diagnosis and a
known mutation for follow-up testing If they test negative, the family history may or may not
still be hereditary but there is no known mutation for follow-up testing
Many sites will start Lynch syndrome testing with a screening test on the colon or endometrial tumor Stored in a wax block at the hospital where you had
surgery
Genetic Testing is done using either a blood sample or a saliva/mouthwash sample
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Genetic Testing:What happens
Costs: Tumor screening tests $500-$1500 Genetic testing $1500/gene or $1500-4500/all genes Known mutation testing $200 - $500
Results: Can take anywhere from 2-12 weeks May be given by telephone or in the setting of post-
test genetic counseling depending on center
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Genetic Testing:Informed Consent Benefits
Know reason for cancers in family Ability to determine who is and who is not at risk Ability to be screened appropriately
Limitations Variants of Uncertain Significance Genes that have not been discovered yet
Risks Bruise from blood draw Psychological risks (guilt from passing gene onto
children, adjustment to testing positive, survival guilt when testing negative)
Insurance discrimination
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove 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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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Refer to an cancer genetic counselor near you Find a Local Counselor from the NSGC
http://nsgc.org/p/cm/ld/fid=164 Find a Local Cancer Genetics expert from the NCI
http://www.cancer.gov/cancertopics/genetics/directory
Refer to a national telecounseling service Informed DNA at http://www.InformedDNA.com 1-800-975-4819
How to find a genetic counselor near you
Heather Hampel
Question & Answer Time . . .
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
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