nov 2012 webinar: lynch syndrome

Welcome! Talking Turkey

About Lynch SyndromePart of Fight Colorectal Cancer’s Monthly Patient Webinar Series

Our webinar will begin shortly

www.FightColorectalCancer.org877-427-2111

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


Fight Colorectal CancerUpcoming 2013 Webinar’s

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Pathways and Targets: How these affect treatment optionsMolecular Testing and Tumor Tissue Testing

Register at www.FightColorectalCancer.org

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Funding Research DirectlyLisa Dubow Fund

http://fightcolorectalcancer.org/research/lisa-fund

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Fight Colorectal CancerDisclaimer

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.


Fight Colorectal CancerResources

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







Lynch Syndrome

Patient

PhysicianGenetics Counselor


Brian Mansfield

Fight Colorectal CancerTo learn more about Brian’s Story:

Downloadable PDF -

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


Fight Colorectal CancerDr. William Harb

Talking Turkey about Lynch Syndrome

Dr. William J. Harb, M.D., FASCRSColorectal Surgeon

Nashville, TN

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

Referred by his internist to a gastroenterologistUndergoes colonoscopyFamily history?

Maternal great-grandfather had colon cancerMaternal uncle with colon cancerQuestionable ovarian cancer in paternal

grandmother and aunt

What next?

A visit to the colorectal surgeonWhat do we talk about?

Review of colonoscopyReview of CT scanDiscussion of colon anatomyDiscussion of family history

Genetic testingWhy? Age under 50Family 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 surgeryIt actually changed what operation he had!

He needs colonoscopy every yearNot every 5 years or 3 yearsNeed to check his stomach Family members need genetic testing

Referral to genetic counselor

SummaryLynch syndrome is not rare

But if you don’t look for it then it won’t be foundWe need the help of patients to discuss this with

their family and their doctorsWe 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

Fight Colorectal CancerHeather Hampel

Talking Turkey about Lynch syndrome

Heather Hampel, MS, CGC

25

The Ohio State University Comprehensive Cancer Center –

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Causes of Hereditary Susceptibility to CRC

Adapted from Burt RW et al. Prevention and Early Detection of CRC, 1996

Sporadic (65%–85%)

Familial (10%–30%)

Lynch syndrome (3%)

Familial adenomatous polyposis (FAP) (1%)

Rare CRC syndromes

(<0.1%)

26



Lynch Syndrome

MLH1

MSH2MSH6

PMS2

27



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

28



Carrier Parent Non-carrier Parent

Aa aa

Aa Aa aa aa

Carrier Carrier Non-carrier Non-carrier

Autosomal Dominant Inheritance

1/2 1/2

29



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

30



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%

31



Surveillance Options for Patients with Lynch syndrome

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

InterventionColonoscopy

Transvaginal ultrasound

Endometrial aspirate

RecommendationBegin at age 20–25,

repeat every 1–2 years

Annually, starting at age 25–35

MalignancyColorectal cancer

Endometrial cancer

32



Surveillance Reduces Risk of Colorectal Cancer in Lynch syndrome Families

Jarvinen HJ et al. Gastro 108:1405, 1995

Years of follow-up

% of subjects

with CRC

30

20

10

4.5%

11.9%

0 3 6 9

SurveillanceNo surveillance

0

33



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.

34



The Family History is Key to Diagnosing Lynch syndrome

CRCdx 45

OvarianCa, dx 64

CRCdx 50s

CRCdx 61

CRCdx 75

CRCdx 48

CRCdx 52

EndometrialCa, dx 59

CRCdx 42

45

35



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

Vasen HFA et al. Gastroenterology 116:1453, 1999

*HNPCC associated cancers: CRC, endometrial, small bowel, ureter, renal pelvis

36



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

37



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+

38



MSI testing on Genotyper

39



Immunohistochemistry

Identify MMR proteins

Normally present If protein is absent,

gene is not being expressed (mutation or methylation)

Helps direct gene testing by predicting likely involved gene

If abnormal IHC (absent), MSI+

MSH2MLH1

MSH6PMS2

40



When to Suspect Hereditary Cancer Syndrome

Cancer in 2 or more close relatives (on same side of family)

Early age at diagnosisMultiple primary tumorsBilateral or multiple rare cancersConstellation of tumors consistent with specific cancer syndrome (eg, breast and ovary)Evidence of autosomal dominant transmission

41



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)

42



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.

43



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

Find a Genetic Counselor www.nsgc.org www.cancer.gov/cancertopics/gene

tics/directory/results

mailto:[email protected]

https://familyhealthlink.osumc.edu/

http://www.nsgc.org/

http://www.cancer.gov/cancertopics/genetics/directory/results

http://www.cancer.gov/cancertopics/genetics/directory/results


Lynch Syndrome

Patient

PhysicianGenetics Counselor

Fight Colorectal CancerResources

To learn more about Lynch Syndrome


5 Questions to Ask your Family at Thanksgiving


Is Lynch Syndrome Lurking in your family worksheet







Fight Colorectal CancerCONTACT US

Fight Colorectal Cancer1414 Prince Street, Suite 204

Alexandria, VA 22314(703) 548-1225

Toll-Free Answer Line: 1-877-427-2111www.FightColorectalCancer.org

Email us: [email protected]

http://www.fightcolorectalcancer.org/

nov 2012 webinar: lynch syndrome

Health & Medicine