vmm

Clinical Management of Families withHereditary Colorectal Cancer SyndromesMonica Dandapani, MS, CGC,* and Elena M. Stoffel, MD, MPH*,†

Hereditary colorectal cancer syndromes can be associated with a lifetime risk of colorectalcancer of >70% in the absence of specialized surveillance. Diagnosing a genetic predis-position to cancer allows clinicians to tailor cancer prevention strategies for patients andfamilies at highest risk. Once a genetic syndrome has been identified in a family, commu-nication with family members, timely implementation of screening tests and/or surgeries,and psychosocial support are all instrumental for effective cancer prevention. Molecularscreening of tumors, computerized risk assessment models, and genetic testing can helpclinicians identify individuals at risk for hereditary cancer syndromes. This review dis-cusses some of the complexities involved in the diagnosis and management of families withhereditary colorectal cancer syndromes and provides strategies for coordinating clinicalcare.

Semin Colon Rectal Surg 22:100-104 © 2011 Elsevier Inc. All rights reserved.

Cancer affects families. Because colorectal cancer (CRC) isthe third most common cancer in the USA, many people

have had a close relative diagnosed with CRC. However, forthe 5-6% of CRC cases associated with hereditary CRC syn-dromes, this diagnosis has profound implications for thefamily and will affect the management of relatives for gener-ations to come. Fortunately, most CRCs are preventable, andthere is good evidence that colonoscopic surveillance reducesmorbidity and mortality from CRC not only in sporadic tu-mors, but also in inherited CRC syndromes.1 However, indi-iduals with a hereditary predisposition to cancer requireore intensive screening than what is routinely recom-ended for close relatives of a patient with sporadic CRC.2-4

In cases of familial adenomatous polyposis (FAP), the risk ofCRC approaches 100% in the absence of endoscopic and/orsurgical intervention and children in families affected withFAP should begin endoscopic screening by age 10 or 11.Lynch syndrome (also known as hereditary nonpolyposisCRC) is the most common hereditary CRC syndrome and isassociated with a lifetime risk of CRC and endometrial cancerof approximately 70% and 40%, respectively.5 Lynch-associ-

*Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston,MA.

†Division of Gastroenterology, Brigham and Women’s Hospital, Boston,MA.

Grant support: NIH-NCI K07 CA 120448-04 Cancer Prevention control,Behavioral and population Sciences Career development Award (EMS).

Address reprint requests to: Elena M. Stoffel, MD, MPH, Smith BuildingRoom 234, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA

02115. E-mail: estoffel@partners.org

100 1043-1489/$-see front matter © 2011 Elsevier Inc. All rights reserved.doi:10.1053/j.scrs.2010.12.008

ated neoplasms often develop at young ages and demonstratean accelerated progression,6,7 justifying annual endoscopicsurveillance beginning as early as age 20,2-4 as well as screen-ing for endometrial cancer for women.8

However, the process by which a family is identified asbeing at high risk can be complex. It requires that a clinicianelicit an accurate family history, recognize the features of thedifferent hereditary cancer syndromes, and recommend therequired colorectal and extracolonic surveillance. In orderfor the full benefit of genetic testing to be realized, the patientmust then effectively communicate this information to mem-bers of the extended family. This review outlines the com-plexities involved in caring for families with hereditary CRCsyndromes and provides some strategies for facilitating theirclinical management.

Challenge 1:Making the Diagnosis ofa Hereditary CRC SyndromePatients with hereditary CRC rarely present with this label. Ifa 30-year-old presents with rectal bleeding and has the classicphenotype of 100s to 1000s of colorectal adenomas, the di-agnosis of FAP may seem obvious. However, if before thediagnosis this patient’s only complaint was that his father hadCRC at age 42, some clinicians may not have recommendeda colonoscopy. Furthermore, if this same 30-year-old wasdiagnosed with CRC in the absence of other adenomas, some

may not suspect a hereditary cancer syndrome at all.

mma

tMatiascnrpit

Clinical management of families with hereditary colorectal cancer syndromes 101

Under ideal circumstances, a patient with a personal orfamily cancer history suspicious for a hereditary CRC syn-drome would be referred for genetic evaluation, undergogenetic testing which revealed a pathogenic gene mutation,and then communicate this information to all at-risk familymembers so they could also be tested to determine whetherthey inherited the genetic predisposition to cancer. However,for many individuals at risk for hereditary CRC syndromes,genetic evaluation is never initiated because clinicians lackinformation regarding other cancer diagnoses in the familyand/or do not recognize the potential for genetic predisposi-tion.9

Lynch syndrome is estimated to account for approximately3-5% of all CRC; yet because this syndrome lacks a distinc-tive phenotype, many of these patients may not be recog-nized as having hereditary CRC. Studies have demonstratedthat fewer than half of individuals with Lynch syndrome havefamily histories that meet the classic Amsterdam Criteria (ini-tially used to define the syndrome).10-12 Furthermore, therevised Bethesda Guidelines may still miss as many as 28% ofmismatch repair (MMR) gene mutation carriers.13-15 BecauseLynch syndrome can be difficult to identify and has impor-tant implications for the surgical management and surveil-lance of CRC patients and their families, experts have pro-posed implementing universal pathology screening of CRCtumors with testing for tumor microsatellite instability (MSI)and immunohistochemical (IHC) expression of MMR pro-teins.15-19 This approach to identifying families with Lynchsyndrome has its limitations, as it depends on (1) having aproband diagnosed with a CRC tumor demonstrating thephenotype of defective MMR, and (2) referring the family forfurther genetic evaluation.20

Nevertheless, often the first individual who seeks geneticevaluation is not a CRC patient, but rather an unaffectedmember of a family in which several people have died ofCRC. In situations in which this “unaffected” individual un-dergoes genetic testing and a pathogenic gene mutation isfound, this confirms the diagnosis in the family. However, amajority of these genetic tests yield results that are eitherclinically indeterminate/uninformative or variants of uncer-tain clinical significance. Having access to detailed informa-tion about ages of diagnosis and types of cancer in the familycan confirm suspicion (or provide reassurance) that a hered-itary cancer syndrome is more (or less) likely.

To collect additional data that might confirm or excludethe possibility of a hereditary cancer syndrome, it may benecessary to involve other family members in the geneticevaluation process.

Consider the following case:

A 36-year female presented for genetic evaluation be-cause of her family history of colon cancer. Her fatherdied of CRC at age 60. With the permission of the de-ceased individual’s wife, the genetic counselor requestedthe father’s medical records to rule out polyposis andreview details of his cancer diagnosis. Pathology recordsindicated that the tumor had been tested with IHC for

MMR proteins and demonstrated absence of expression

of the MLH1 protein. A doctor’s note documented a dis-cussion encouraging his CRC patient to undergo a ge-netic evaluation, but this was never completed. In light ofthis information, the unaffected young woman opted toundergo genetic testing for Lynch syndrome, which didnot reveal any mutations in MLH1, MSH2, or MSH6genes and was clinically indeterminate. The geneticsteam encouraged the patient to contact her father’s sis-ter. This individual had recently been diagnosed withendometrial cancer and the genetics team coordinatedher genetic testing, which revealed a pathogenic muta-tion in MLH1, confirming the family’s diagnosis ofLynch syndrome and changing the unaffected youngwoman’s genetic test result from “indeterminate” to“true negative.”

Knowledge of a true positive genetic test result in a surviv-ing cancer-affected relative can help clinicians reinterpret themeaning of a test result that might otherwise be clinicallyuninformative. Furthermore, confirming the presumed diag-nosis of a hereditary cancer syndrome gives other familymembers the opportunity to undergo informative genetictesting to stratify their cancer risk. In cases in which testingyields a genetic variant of uncertain clinical significance,reaching out to family members is essential. Does the varianttrack with cancer in the family? Is there another pathogenicmutation known in the family? Eventually, information mayemerge to reclassify the variant as either pathogenic or benign(polymorphism) through molecular assays21,22; however, this

ay take years, during which time clinicians will have toake decisions regarding how best to manage individuals

t-risk.In classic FAP, genetic testing reveals a pathogenic muta-

ion in the APC gene in 90% of cases. Biallelic mutations inYH can produce a similar polyposis phenotype (albeit with

n autosomal-recessive pattern of inheritance); however,here remain some families who have clinical FAP without andentified genetic mutation. For other syndromes, such asttenuated polyposis, juvenile polyposis, and Peutz–Jeghersyndrome, genetic testing may be informative in only 50% ofases. In these cases it is important to understand that aegative genetic test does not exclude the diagnosis of a he-editary cancer syndrome; it merely means that the option ofredictive genetic testing will not be available to other at-risk

ndividuals, who will need to be managed as if they are po-entially affected.

Challenge 2: FamilyCommunication AboutInherited Cancer SyndromesEven under the best of circumstances, communicationamong family members can be complicated. When the sub-ject matter is cancer, conversations can become emotionallycharged, and some family members may refuse to even talkabout cancer.23

Consider the following case:

cGhthaAcOLer

tt

btvfs

ambsdtfm

102 M. Dandapani and E.M. Stoffel

A 50-year-old man presented to a colorectal surgeonwith his second diagnosis of CRC, after having beendiagnosed with his first CRC 20 years prior. The patienthad been undergoing colonoscopies every 5 years. Thesurgeon recognized the patient’s last name and realizedhe had previously operated on this patient’s cousin whohad also been diagnosed with CRC at a young age. Al-though the patient knew that his cousin had been diag-nosed with CRC, he was not aware that his cousin hadundergone genetic testing that revealed that he carried apathogenic MMR gene mutation associated with Lynchsyndrome. Because of privacy laws, the surgeon couldnot disclose the information about the cousin’s geneticdiagnosis to his patient, but he did refer him for geneticevaluation.

Unfortunately, information about genetics and heredi-tary cancer syndromes can be difficult for patients to un-derstand, and even more challenging to explain to theirfamily members. Privacy rules prevent clinicians fromcontacting a patient’s relatives to disclose genetic test re-sults.24 Professional societies (including the American So-iety for Human Genetics, American College of Medicalenetics, and the American Society for Clinical Oncology)ave concluded that the ethical duty to warn is satisfied ifhe clinician informs the patient that the genetic conditionas implications for the health of other family membersnd encourages the patient to tell relatives of these risks.s a result, patients are often left to communicate thisomplicated information to family members themselves.ur survey of individuals undergoing genetic testing forynch syndrome demonstrated that 1 in 4 mutation carri-rs did not share information about their test result withelatives beyond their immediate family.25 In most cases,

individuals reported that they did not deliberately decideto withhold the information; however, they were “notclose” with specific family members, were concerned thatthey would not be able to explain the genetic informationeffectively, and/or were concerned that their family mem-bers would worry or not understand the relevance of theinformation to their own health. These barriers have alsobeen reported by other studies of family communica-tion,26-28 including a recent study looking at communica-ion between parents affected with Lynch syndrome andheir offspring.29

While these barriers to communication in families may besignificant, they can be overcome.30 Several studies havedemonstrated that individuals prefer the involvement ofhealth care workers in the process of family communica-tion.29,31 Genetic counselors are trained to help individualsnavigate challenges involved in disseminating informationabout genetic testing. Pre- and posttest counseling, providingsummary letters for patients to distribute to family members,coordinating permissions for release of medical information,and organizing referrals for family members who may live faraway can all be helpful for ensuring effective communication

about genetic risk.

Challenge 3: EffectiveCancer PreventionThe ultimate goal of genetic testing for hereditary CRC is toprevent cancers in a family through endoscopic and surgicalinterventions. Models have shown that extending the benefitsof genetic testing to other relatives makes it even more cost-effective.32,33 However, in order for this information to be of

enefit, it must be communicated to the family member, andhen the family members must inform their health care pro-iders. Studies have shown that many clinicians may not beamiliar with the management of different hereditary canceryndromes.34,35 Furthermore, until a genetic test result de-

fines the syndrome in the family, individuals at risk for he-reditary CRC are often not screened as rigorously as theyshould be.36 In addition to frequent CRC surveillance, it isimportant to realize the need to screen for the various extra-colonic cancers associated with many of these hereditary syn-dromes (Lynch syndrome—endometrial and ovarian cancer;Peutz–Jeghers syndrome—breast, pancreas, and gynecologiccancers; FAP—duodenal, ampullary and thyroid cancers),which may require referrals to other specialists.8

Knowledge that there is a hereditary syndrome in the fam-ily could impact the management of individuals diagnosedwith polyps or cancers. Because the risk for metachronousCRC in Lynch syndrome is high, patients diagnosed withLynch-associated CRC may benefit from subtotal colectomyrather than segmental resection.37 The patient with 20-30denomatous polyps removed during yearly colonoscopiesay opt to have a total colectomy if the diagnosis of FAP has

een made in another family member. Unfortunately, inome families with FAP the death of a parent or sibling is soevastating that at-risk relatives remain in denial about ownheir risks and the need for increased surveillance. In theseamilies, making a decision about a risk-reducing colectomyay require additional presurgical counseling.38

It can be helpful to provide patients with a detailed letteroutlining specific cancer screening recommendations for pa-tients as well as their relatives who are also at-risk for thehereditary cancer syndrome. Patients should be encouragedto share this letter with their physicians and family members.When patients give providers permission to discuss the fam-ily history and genetic test result, this can allow differentclinicians caring for a family to communicate directly, whilestill abiding by privacy requirements.

Challenge 4:Support of Families withHereditary SyndromesOne should not overlook the emotional impact that heredi-tary cancer risk may have on an individual. Psychosocialdistress is not uncommon for individuals with these syn-dromes and has been well documented in the FAP popula-tion.39 More recent studies have found similar distress amongindividuals with Peutz–Jeghers syndrome,40 and 1 study of

individuals at risk for Lynch syndrome demonstrated a ten-

psfba

Clinical management of families with hereditary colorectal cancer syndromes 103

dency toward risky health behaviors, such as smoking, alco-hol use, and unhealthy diet.41 Many patients may not appre-ciate that the diagnosis of a hereditary cancer syndrome doesnot represent a “death sentence,” and genetic counseling mayprovide an appropriate venue for a discussion about risk-reducing behavioral modification.42,43

Many families want to know when their children shouldundergo genetic testing. Genetic testing is considered inchildhood for syndromes that manifest in childhood, includ-ing FAP, Peutz–Jeghers syndrome, and juvenile polyposissyndrome, because this information would influence medicalmanagement. In contrast, for Lynch syndrome there is noreason to consider genetic testing before age 18-20, sinceCRC surveillance is rarely indicated before age 20. Genetictesting in childhood is ethically challenging for providers andtheir young patients who may suffer psychological distressrelated to knowledge about genetic risk.44,45 Similarly, differ-ent adult family members may respond differently to newsabout a genetic risk, and some may require more psychoso-cial support throughout the process. Parents may feel guiltyabout passing a gene mutation to their child, or a person whotests negative for the mutation present in the family mayexperience survivor guilt. These issues can be managed withappropriate pre- and posttest counseling.

Finally, the needs of the patient and his/her family mem-bers do change as the family ages, as the next generation startsto have children, and the family tree grows. Several studieshave shown that some individuals at risk for hereditary can-cer syndromes may be interested in the option of using pre-natal testing and/or assisted reproductive technologies, suchas preimplantation diagnosis, to reduce the risk of passing onthe gene mutation in future pregnancies.46,47

Future DirectionsThe human genome project has given rise to the promise ofpersonalized medicine. In an effort to screen for hereditaryCRC, many institutions have already begun to screen all colo-rectal tumors for evidence of MSI and/or IHC looking fordeficient MMR associated with Lynch Syndrome. In somecenters, the result of this “routine” screening is reported as anaddendum at the bottom of the surgical pathology reportreturned to the surgeon.

Consider the following case:

A patient diagnosed with stage II CRC over a year agohad surgery at 1 institution and then went to a differentpractice for his oncology care. The oncologist neverlearned of the abnormal MMR protein expression thatwas reported as an addendum on the revised surgicalpathology report. The oncologist claimed that she wouldhave made different recommendations about adjuvantchemotherapy had she known that the patient had Lynchsyndrome.

Approximately 15% of CRC tumors will demonstrate MSI.Most of these will be due to epigenetic changes and not toLynch syndrome, but this cannot be determined without fur-

ther testing (BRAF V600E mutation or MLH1 promoter hy-

ermethylation are common causes of MSI). Routine tumorcreening will raise this question of inherited predispositionor many more CRC patients, and their families, placing theurden on clinicians to interpret and use this informationppropriately.48 Many institutions are working to develop

strategies for supporting both patients and providers whenabnormal results appear. Cancer centers that have estab-lished registries for hereditary CRC syndromes can be helpfulin providing expert resources to clinicians, patients, and fam-ilies.

ConclusionsThe clinical management of families with hereditary CRC canbe complex. Even when the diagnosis of genetic predisposi-tion is suspected, confirming the diagnosis may be difficult.When a gene mutation associated with cancer predispositionis identified in a family, genetic counseling may help facilitatefamily communication and compliance with recommenda-tions for cancer prevention.

References1. Jarvinen HJ, Aarnio M, Mustonen H, et al: Controlled 15-year trial on

screening for colorectal cancer in families with hereditary nonpolyposiscolorectal cancer. Gastroenterology 118:829-834, 2000

2. Lindor NM, Petersen GM, Hadley DW, et al: Recommendations for thecare of individuals with an inherited predisposition to Lynch syn-drome: A systematic review. JAMA 296:1507-1517, 2006

3. Burt RW, Barthel KS, Dunn KB, et al: NCCN Clinical Practice Guide-lines in Oncology: Colorectal Cancer Screening. J Natl Compr CancNetw 8:8-61, 2010

4. Vasen HF, Moslein G, Alonso A, et al: Guidelines for the clinical man-agement of Lynch syndrome (hereditary non-polyposis cancer). J MedGenet 44:353-362, 2007

5. Stoffel EM, Mukherjee B, Raymond VM, et al: Calculation of risk ofcolorectal and endometrial cancer among patients with Lynch syn-drome. Gastroenterology 137:1621-1627, 2009

6. Vasen HF, Nagengast FM, Khan PM: Interval cancers in hereditarynon-polyposis colorectal cancer (Lynch syndrome). Lancet 345:1183-1184, 1995

7. Jass JR, Stewart SM: Evolution of hereditary non-polyposis colorectalcancer. Gut 33:783-786, 1992

8. Jasperson KW, Tuohy T, Neklason DW, et al: Hereditary and familialcolon cancer. Gastroenterology 138:2044-2058, 2010

9. Weissman SM, Bellcross C, Bittner CC, et al: Genetic counseling con-siderations in the evaluation of families for Lynch syndrome---A re-view. J Genet Couns 2010 [Epub ahead of print]

10. Heinimann K, Scott RJ, Buerstedde JM, et al: Influence of selectioncriteria on mutation detection in patients with hereditary nonpolyposiscolorectal cancer. Cancer 85:2512-2518, 1999

11. Nyström-Lahti M, Wu Y, Moisio AL, et al: DNA mismatch repair genemutations in 55 kindreds with verified or putative hereditary non-polyposis colorectal cancer. Hum Mol Genet 5:763-769, 1996

12. Syngal S, Fox EA, Eng C, et al: Sensitivity and specificity of clinicalcriteria for hereditary non-polyposis colorectal cancer associated mu-tations in MSH2 and MLH1. J Med Genet 37:641-645, 2000

13. de la Chapelle A, Palomaki G, Hampel H: Identifying Lynch syndrome.Int J Cancer 125:1492-1493, 2009

14. Umar A, Boland CR, Terdiman JP, et al: Revised Bethesda Guidelinesfor hereditary nonpolyposis colorectal cancer (Lynch syndrome) andmicrosatellite instability. J Natl Cancer Inst 96:261-268, 2004

15. Hampel H, Frankel W, Martin E, et al: Feasibility of screening for Lynchsyndrome among patients with colorectal cancer. J Clin Oncol 26:5783-5788, 2008

16. Hampel H, Frankel W, Panescu J, et al: Screening for Lynch syndrome

1

1

1

2

2

2

2

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

3

4

4

4

4

4

4

4

4

4

104 M. Dandapani and E.M. Stoffel

(hereditary nonpolyposis colorectal cancer) among endometrial cancerpatients. Cancer Res 66:7810-7817, 2006

7. Hampel H, Frankel W, Martin E, et al: Screening for the Lynch syn-drome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352:1851-1860, 2005

8. Hampel H, Pancescu J, Lockman J, et al: Comment on: Screening forLynch syndrome (hereditary nonpolyposis colorectal cancer) amongendometrial cancer patients. Cancer Res 67:9603, 2007

9. Point HH: Justification for Lynch syndrome screening among all pa-tients with newly diagnosed colorectal cancer. J Natl Compr CancerNetw 8:597-601, 2010

0. Hall MJ: Counterpoint: Implementing population genetic screening forLynch syndrome among newly diagnosed colorectal cancer patients—Will the ends justify the means? J Natl Compr Cancer Netw 8:606-611,2010

1. Kohonen-Corish M, Weber TK, Lindblom A, et al: Report of the Com-bined Meeting of the International Society for Gastrointestinal Hered-itary Tumours, the Human Variome Project and the National CancerInstitute Colon Cancer Family Registry, Düsseldorf, Germany. FamCancer 9:705-711, 2010

2. Spurdle AB: Clinical relevance of rare germline sequence variants incancer genes: evolution and application of classification models. CurrOpin Genet Dev 20:315-323, 2010

3. Gaff CL, Clarke AJ, Atkinson P, et al: Process and outcome in commu-nication of genetic information within families: A systematic review.Eur J Hum Genet 15:999-1011, 2007

4. Offit K, Groeger E, Turner S, et al: The “duty to warn” a patient’s familymembers about hereditary disease risks. JAMA 292:1469-1473, 2004

5. Stoffel EM, Ford B, Mercado RC, et al: Sharing genetic test results inLynch syndrome: Communication with close and distant relatives. ClinGastroenterol Hepatol 6:333-338, 2008

6. Chivers-Seymour K, Addington-Hall J, Lucassen AM, et al: What facil-itates or impedes family communication following genetic testing forcancer risk? A systematic review and meta-synthesis of primary quali-tative research. J Genet Couns 19:330–342, 2010

7. Mesters I, Ausems M, Eichhorn S, et al: Informing one’s family aboutgenetic testing for hereditary non-polyposis colorectal cancer (HN-PCC): A retrospective exploratory study. Fam Cancer 4:196-197, 2005

8. Carlsson C, Nilbert M: Living with hereditary non-polyposis colorectalcancer; experiences from and impact of genetic testing. J Genet Couns16:811-820, 2007

9. Aktan-Collan KI, Kaariainen HA, Kolttola EM, et al: Sharing geneticrisk with next generation: Mutation-positive parents’ communicationwith their offspring in Lynch syndrome. Fam Cancer 2010 [Epub aheadof print]

0. Peterson SK, Watts BG, Koehly LM, et al: How families communicateabout HNPCC genetic testing: Findings from a qualitative study. Am JMed Genet C Semin Med Genet 119C:78-86, 2003

1. Pentz RD, Peterson SK, Watts B, et al: Hereditary nonpolyposis colo-

rectal cancer family members’ perceptions about the duty to inform and

health professionals’ role in disseminating genetic information. GenetTest 9:261-268, 2005

2. Ramsey SD, Clarke L, Etzioni R, et al: Cost-effectiveness of microsatel-lite instability screening as a method for detecting hereditary nonpol-yposis colorectal cancer. Ann Intern Med 135:577-588, 2001

3. Mvundura M, Grosse SD, Hampel H, et al: The cost-effectiveness ofgenetic testing strategies for Lynch syndrome among newly diagnosedpatients with colorectal cancer. Genet Med 12:93-104, 2010

4. Batra S, Valdimarsdottir H, McGovern M, et al: Awareness of genetictesting for colorectal cancer predisposition among specialists in gastro-enterology. Am J Gastroenterol 97:729-733, 2002

5. Schroy PC 3rd, Barrison AF, Ling BS, et al: Family history and colorec-tal cancer screening: A survey of physician knowledge and practicepatterns. Am J Gastroenterol 97:1031-1036, 2002

6. Stoffel EM, Mercado RC, Kohlmann W, et al: Prevalence and predictorsof appropriate colorectal cancer surveillance in Lynch syndrome. Am JGastroenterol 105:1851-1860, 2010

7. Kalady MF, McGannon E, Vogel JD, et al: Risk of colorectal adenomaand carcinoma after colectomy for colorectal cancer in patients meetingAmsterdam criteria. Ann Surg 252:507-511, 2010

8. Neuman HB, Robbins L, Duarte J, et al: Risk-reducing surgery in FAP:Role for surgeons beyond the incision. J Surg Oncol 101:570-576,2010

9. Douma KF, Aaronson NK, Vasen HF, et al: Psychological distress anduse of psychosocial support in familial adenomatous polyposis. Psy-chooncology 19:289-298, 2010

0. van Lier MG, Mathus-Vliegen EM, van Leerdam ME, et al: Quality of lifeand psychological distress in patients with Peutz–Jeghers syndrome.Clin Genet 78:219-226, 2010

1. Burton AM, Peterson SK, Marani SK, et al: Health and lifestyle behav-iors among persons at risk of Lynch syndrome. Cancer Causes Control21:513-521, 2010

2. Biesecker BB, Marteau TM: The future of genetic counseling: An inter-national perspective. Nat Genet 22:131-137, 1999

3. Lawson P, Flocke S: Teachable moments for health behavior change: Aconcept analysis. Patient Educ Couns 76:25-30, 2009

4. Duncan RE, Gillam L, Savulescu J, et al: The challenge of developmen-tally appropriate care: Predictive genetic testing in young people forfamilial adenomatous polyposis. Fam Cancer 9:27-35, 2010

5. Mireskandari S, Sangster J, Meiser B, et al: Psychosocial impact offamilial adenomatous polyposis on young adults: A qualitative study.J Genet Couns 18:409-417, 2009

6. Douma KF, Aaronson NK, Vasen HF, et al: Attitudes toward genetictesting in childhood and reproductive decision-making for familialadenomatous polyposis. Eur J Hum Genet 18:186-193, 2009

7. Kastrinos F, Stoffel EM, Balmana J, et al: Attitudes toward prenatalgenetic testing in patients with familial adenomatous polyposis. Am JGastroenterol 102:1284-1290, 2007

8. Stoffel EM, Chittenden A: Genetic testing for hereditary CRC: Chal-lenges in identifying, counseling, and managing high-risk patients.

Gastroenterology 139:1436-1441, 2010