Nov 2012 Webinar: Lynch Syndrome

Welcome!
Talking Turkey
About Lynch Syndrome
Part of Fight Colorectal Cancer’s Monthly Patient Webinar Series

Our webinar will begin shortly

www.FightColorectalCancer.org
877-427-2111

Fight Colorectal Cancer
1. Tonight’s speaker’s: Brian Mansfield, Dr. William Harb, and
Heather Hampel

2. Archived webinars: Link.FightCRC.org/Webinars

3. Follow up survey to come via email. Get a free Blue Star of
Hope pin when you tell us how we did tonight.

4. Ask a question in the panel on the right side of your screen

5. Or call the Fight Colorectal Cancer Answer Line at 877-427-2111

877-427-2111

Upcoming 2013 Webinar’s

Advancements in CRC Surgery
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Management of Peripheral Neuropathy
Pathways and Targets: How these affect treatment options
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Register at
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Funding Research Directly
Lisa Dubow Fund
http://fightcolorectalcancer.org/research/lisa-fund

Disclaimer

The information and services provided by Fight Colorectal
Cancer are for general informational purposes only.

The information and services are not intended to be substitutes
for professional medical advice, diagnosis, or treatment.

If you are ill, or suspect that you are ill, see a doctor
immediately. In an emergency, call 911 or go to the nearest
emergency room.

Fight Colorectal Cancer never recommends or endorses any
specific physicians, products or treatments for any condition.
877-427-2111

Resources

To learn more about Lynch Syndrome

http://fightcolorectalcancer.org/awareness/lynch_syndrome

5 Questions to Ask your Family at Thanksgiving

http://fightcolorectalcancer.org/images/posts/2012/10/5-
Questions.pdf

Is Lynch Syndrome Lurking in your family worksheet

http://fightcolorectalcancer.org/images/posts/2012/10/Lynch-
lurking.pdf


Patient

Lynch
Syndrome

Genetics
Physician
Counselor


Brian Mansfield

To learn more about Brian’s Story:

Downloadable PDF -

http://fightcolorectalcancer.org/images/posts/
2012/10/Lynch-article-FINAL.pdf

877-427-2111

Dr. William Harb

Talking Turkey about
Lynch Syndrome
Dr. William J. Harb, M.D., FASCRS
Colorectal Surgeon
Nashville, TN

 48 year old male presents with a change in his bowel
habits

 Referred by his internist to a gastroenterologist
 Undergoes colonoscopy
 Family history?
 Maternal great-grandfather had colon cancer
 Maternal uncle with colon cancer
 Questionable ovarian cancer in paternal grandmother and
aunt

 A visit to the colorectal surgeon
 What do we talk about?
 Review of colonoscopy
 Review of CT scan
 Discussion of colon anatomy
 Discussion of family history

 Genetic testing
 Why?
 Age under 50
 Family history
 Often unreliable as in Brian’s case – many physicians would
think that maternal great-grandfather and uncle not related
closely enough
 Ovarian cancer often neglected in family history

 Brian had genetic testing prior to surgery
 It actually changed what operation he had!

 He needs colonoscopy every year
 Not every 5 years or 3 years
 Need to check his stomach
 Family members need genetic testing
 Referral to genetic counselor

Summary
 Lynch syndrome is not rare
 But if you don’t look for it then it won’t be found
 We need the help of patients to discuss this with their
family and their doctors
 We can prevent colon cancer with genetic testing
 And we can prevent people like Brian from having to go thru
this ordeal
 Please talk to your doctors and your family – the holidays
are a great time of year to talk about medical history

Heather Hampel

Talking Turkey about
Lynch syndrome
Heather Hampel, MS, CGC

Causes of Hereditary Susceptibility to
CRC

Sporadic
(65%–85%)
Familial
(10%–30%)

Rare CRC
syndromes Lynch syndrome (3%)
(<0.1%)
Familial adenomatous
polyposis (FAP) (1%)
Adapted from Burt RW et al. Prevention and Early Detection of CRC, 1996
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute 25

Lynch Syndrome

MSH2
MSH6

MLH1

PMS2


Sporadic Inherited
Normal gene Germline
mutation
Somatic
mutation
Somatic
mutation

Somatic
mutation

• Later age at onset (60s or 70s) •Early age at onset (<50)
• Little or no family history of cancer •Multiple generations with
cancer
• Single or unilateral tumors
•Clustering of certain cancers
(i.e. breast/ovarian)

Autosomal Dominant Inheritance
Carrier Parent Non-carrier Parent

Aa aa

Aa Aa aa aa

Carrier Carrier Non-carrier Non-carrier

1/2 1/2

Clinical Features of 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


Lynch Syndrome Cancer Risks (to 70)
Cancer MLH1& MSH2 MSH6 PMS2

♂ Colon cancer 56% - 85% 22% 20%

♀ Colon cancer 48% - 85% 10% 15%

Endometrial cancer 35% - 64% 26% 15%

♂ Other LS cancers 19.3% 3% 6%

♀ Other LS cancers 5% 11% 6%

Surveillance Options for Patients with
Lynch syndrome

Malignancy Intervention Recommendation
Colorectal cancer Colonoscopy Begin at age 20–25,
repeat every 1–2
years
Endometrial  Transvaginal Annually, starting at
cancer ultrasound age 25–35
 Endometrial
aspirate

Lindor NM, et al. JAMA 2006;296(12):1507-1517.

Surveillance Reduces Risk of Colorectal
Cancer in Lynch syndrome Families
30
No surveillance
% of Surveillance
subjects 20
with CRC
11.9%
10

4.5%
0
0 3 6 9
Years of follow-up
Jarvinen HJ et al. Gastro 108:1405, 1995

Prophylactic Surgery Options for
Patients with Lynch syndrome

 Options include subtotal colectomy,
hysterectomy, and oophorectomy
 Surgery does not eliminate cancer risk
 Recent data that hysterectomy with BSO
eliminates the risk of endometrial and ovarian
cancer in LS patients

Schmeler KM, et al. NEJM 2006;354:261-269.

The Family History is Key to Diagnosing
Lynch syndrome

CRC
dx 50s

CRC CRC
CRC dx 61 dx 75 Ovarian
dx 45 Ca, dx 64

CRC CRC Endometrial 45 CRC
dx 48 dx 52 Ca, dx 59 dx 42

Amsterdam Criteria II

 3 or more relatives with verified HNPCC-
associated cancers* in family
 One case a first-degree relative of the other two
 Two or more generations
 One CRC by age 50
 FAP excluded

*HNPCC associated cancers: CRC, endometrial, small bowel,
ureter, renal pelvis
Vasen HFA et al. Gastroenterology 116:1453, 1999

Genetic Features of Lynch Syndrome

 Genes belong to DNA mismatch repair
(MMR) family
 Mutations in MMR genes lead to
microsatellite instability
 MMR proteins are missing in the tumor
tissue making immunohistochemical staining
useful


Microsatellite Instability (MSI)

 Repetitive DNA sequences 1- 4 nucleotides
(microsatellites) normally found genome
 Mono: TCGAGG AAAAAAAA GGAGCT
 Di: TCGAGG CACACACACACA GGAG
 With MMR failure, variability in repeats
 90% of HNPCC tumors are MSI+
 10%–15% of sporadic CRCs are MSI+


MSI testing on Genotyper


Immunohistochemistry

 Identify MMR
proteins
 Normally present
 If protein is absent,
gene is not being
expressed (mutation
MLH1 MSH2
or methylation)
 Helps direct gene
testing by predicting
likely involved gene
 If abnormal IHC
(absent), MSI+

PMS2
MSH6

When to Suspect Hereditary Cancer
Syndrome
Cancer in 2 or more close relatives
(on same side of family)
Early age at diagnosis
Multiple primary tumors
Bilateral or multiple rare cancers
Constellation of tumors consistent with specific
cancer syndrome (eg, breast and ovary)
Evidence of autosomal dominant transmission

When Should Genetic Testing Be
Considered?

 Significant family cancer history
 Reasonable likelihood of carrying an altered
cancer susceptibility gene
 Ideally, test affected person first
 Results will influence medical management
 Patient wants information (empowerment)


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.


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
 Find a Genetic Counselor
 www.nsgc.org
 www.cancer.gov/cancertopics/gen
etics/directory/results



877-427-2111

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(703) 548-1225
Toll-Free Answer Line: 1-877-427-2111

Email us: Info@FightColorectalCancer.org

Nov 2012 Webinar: Lynch Syndrome

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