Fandom

Psychology Wiki

Genetic counseling: Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

34,203pages on
this wiki
Add New Page
Talk0 Share

Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Clinical: Approaches · Group therapy · Techniques · Types of problem · Areas of specialism · Taxonomies · Therapeutic issues · Modes of delivery · Model translation project · Personal experiences ·


Lynch Syndrome /

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

ContractingEdit

  • Introductions
  • What are your main concerns? What do you hope to learn today?
  • What do you know about colon cancer?

Review Family and Medical HistoryEdit

  • Medical History
    • How have you gotten to this point?
    • Screening practices?
    • Other significant illnesses, hospitalizations?
  • Family History
    • Other individuals with any type of cancer?
    • If affected:
      • Age and date at diagnosis, death
      • Current age
      • Type, location, stage of primary cancer
      • Secondary cancer - metastasis or new primary
      • Environmental exposures
    • If unaffected:
      • Current age
      • Health and history of illness
      • If deceased, cause and age at death
    • Screening practices
    • Family thoughts on cause of cancer?

Colon CancerEdit

  • Third leading cause of cancer in men and women
    • 9% of new cancer diagnoses, 11% of all cancer deaths
    • Incidence is over 160,000 new cases of colon and rectal cancer per year
    • About 5-10% of all colorectal cancers are hereditary
      • 3-7% due to Lynch Syndrome / HNPCC
      • 1% due to FAP
    • About 10-30% of colorectal cancers are familial
    • Average diagnosis is age 44
  • Caused by uncontrolled proliferation of cells in colon or rectum
    • Symptoms may include blood in stool, diarrhea, constipation, reflux, stomach cramps, frequent bloating, weight loss, or unusual and continuing lack of energy
    • Cancer cells may enter blood or lymphatic system and metastasize to form secondary tumors in other parts of body
  • Multifactorial disorder involving both genetic and non-genetic factors
    • Non-genetic factors
      • Diet: high fat, low fiber, high red meat intake, not enough fresh foods, processed foods
      • Colorectal polyps (adenomatous polyps)
      • Alcohol, cigarettes
      • Chronic disease of bowel (Crohn's disease, inflammatory bowel disease, ulcerative colitis)
      • Obesity
    • Genetic factors
      • Hereditary colorectal cancer syndromes
        • HNPCC and FAP
        • Rare colorectal syndromes: Peutz-Jeghers Syndrome, Juvenile Polyposis Coli
  • Lynch Syndrome Cancers
    • Colon Cancer
    • Endometrial Cancer
  • Lynch Syndrome Cancers
    • Colon Cancer
    • Endometrial Cancer
  • Ovarian Cancer
  • Gastric Cancers
  • Hepatobiliary Cancers
  • Renal Pelvic Cancer
  • Pancreatic Cancer
  • Skin Cancers (Muir Torre)
  • Brain Cancer

Genetic Etiology of Hereditary Colon CancerEdit

  • Autosomal dominant inheritance
    • Each child of mutation carrier has 50% chance of inheriting mutation
    • Mutations in DNA mismatch repair genes
      • MSH2 at 2p22
      • MLH1 at 3p21
      • PMS1 at 2q31
      • PMS2 at 7p22
      • MSH6 at 2p16
      • Other more rare genes
      • 60% of HNPCC due to mutations in MSH2 or MLH1
    • Carcinogenesis due to loss of heterozygosity of one of genes above
      • Causes defective mismatch repair
      • Mutations accumulate throughout the genome
    • Microsatellite instability (MSI)
      • Provides indirect evidence for presence or absence of germline mutation
      • Due to genome wide instability of replication and repair of repeat sequences
      • 10-15% of sporadic tumors show MSI, >95% of HNPCC tumors show MSI
  • Penetrance variable - use lifetime cancer risks for mutation carriers
    • Mutation also increases risk for other types of cancer besides colorectal cancer
    • 30% risk of second primary 10 years after original diagnosis
    • 50% risk of second primary 15 years after original diagnosis


Lifetime Risks for HNPCC-Related Cancers
Site Population Risk Hereditary Risk
Colon/Rectum 5% 70-80%
Endometrium 1.5% 60%
Ovarian 2% 9%
Urinary Tract (Kidney and Ureter) <1% 10%
Stomach <1% 19%
Small Intestine <1% <5%

Cancer Risk AssessmentEdit

  • Features of hereditary colorectal cancer
    • More than one generation affected
    • Early age at diagnosis
    • Bilateral or multiple primary cancers
    • Combination of tumors consistent with specific cancer syndrome
  • Strengths and limitations of cancer risk assessment
    • Knowledge of family history may be limited
    • Cancer occurs with or without hereditary cancer syndrome
    • Can't diagnose on the basis of family history information alone
  • Features associated with HNPCC
    • Polyps present in small numbers or not at all
    • Proximal (right-sided) colon cancer
    • Mean age at diagnosis is 45 years
  • Individual risk based on personal/family history: ________
  • Muir-Torre Syndrome
    • Variant of HNPCC
    • Associated with MSH2 or MLH1 mutations
    • Typical features of HNPCC
    • Also includes sebaceous gland tumors and keratoacanthomas
  • Turcot Syndrome
    • Rare hereditary syndrome of multiple colorectal adenomas and brain tumors
    • Two subtypes
      • APC mutations associated with medulloblastomas
      • MMR mutations associated with glioblastomas

Genetic TestingEdit

  • Diagnostic/Testing Criteria for HNPCC
    • Amsterdam Criteria
      • Family must meet ALL of the following
        • Three cases of colorectal cancer
        • One affected person is first-degree relative of other two
        • Two successive generations affected
        • One diagnosis < 40 years
        • FAP excluded in cases of colon cancer
        • Tumors verified by pathology
      • Failure to meet these criteria DOES NOT exclude HNPCC
    • Modified Amsterdam Criteria
      • Family must meet ALL of the following
        • Three relatives with HNPCC-related cancer
        • One person is first-degree relative of other two
        • Two successive generations affected
        • One diagnosis < 50 years
        • FAP excluded in cases of colon cancer
        • Tumors verified by pathology
      • HNPCC-related cancers include colorectal, endometrial, small bowel, ureter, renal pelvis)
    • Bethesda Guidelines for eligibility for MSI testing
      • Family or proband meets at least one criteria
        • Family fits either Amsterdam criteria
        • Proband has two HNPCC-related cancers
        • Proband has CRC plus 1st degree relative with HNPCC-related cancer or CRC adenoma <45 years
        • Colorectal or endometrial cancer diagnosed before 45 years
        • Right-sided colon cancer if undifferentiated diagnosed before 45 years
        • Signet-ring cell type colorectal diagnosed before 45 years
        • Colon adenomas diagnosed before 45 years
      • If high MSI, proceed to germline mutation testing
      • Bethesda Revised Guidelines
      • 1. The patient is younger than age 50.
        2. The patient has multiple HNPCC-associated tumors in the colon or in other areas known to be caused by the same mutations, either at the same time or occurring over a period of time.
        3. A patient younger than age 60 has colorectal cancer that has microscopic characteristics that are often indicative of MSI.
        4. A patient has one or more first-degree relatives who had an HNPCC-related tumor at age 50 or younger.
        5. A patient has two or more first- or second-degree relatives who had HNPCC-related tumors at any age.
  • Common adult cancers may be due to one of several genes or genetic and environmental interactions
    • Negative result difficult to interpret since it can be more than one gene
    • Preferable to identify mutation in relative with cancer before testing other at-risk relatives
    • General population screening not appropriate for this reason
    • DNA banking is option to defer testing until sometime in future
  • Testing procedures
    • Process
      • Blood drawn here and sent to outside lab (Myriad)
      • Results usually take about 4 weeks
    • Payment methods
      • Patient pay with check, money order, credit card
      • Insurance claims
        • Submit patient insurance authorization with sample
        • Requires 20% copay or insurance verified patient portion
      • Medicare claims - Medicare Waiver of Liability required
      • Institutional pay - Myriad bills institution directly
    • Current prices
      • Comprehensive COLARIS (MLH1 and MSH2 sequencing) $1950
      • Single Site COLARIS (known family mutation) $315
      • Micorsatellite Instabilty $600
        • Used to screen before DNA testing
        • Must be done on tumor tissue
        • Cannot be billed to insurance
    • Practice guidelines for testing
      • If positive for Bethesda criteria, start with MSI
      • If MSI high, consider genetic testing
      • If MSI low or negative, consider testing if Amsterdam positive
      • If Bethesda and Amsterdam negative, manage based on family history
  • Mutation identified
    • Increased risk for cancer
    • Gene could be passed on to children
    • Other at-risk relatives should be informed and offered counseling
    • Important to establish management plan
    • Insurance issues
  • Mutation not identified
    • Inherited cancer can't be ruled out since mutation may have been missed or exist in another gene
    • May be no genetic explanation for cancer in family
    • Person with cancer who does not have mutation may be sporadic case
    • Relatives may still be at risk and should discuss family history with their doctor
  • Limitations of testing
    • Can't predict when a person with a mutation will develop cancer
    • Not all persons with mutation will develop cancer
    • Some mutations may be missed or can't be interpreted
    • Efficacy of screening for some related cancers (eg ovarian) is unknown
  • Benefits of testing
    • May provide information
      • Explanation for cancer in family
      • Increased surveillance or plan for future
      • Clarify risks to children and other family members
    • Reassurance
    • Colon surveillance in at risk persons proven to reduce mortality
  • Risks of testing
    • Insurability
    • Employment issues
    • Confidentiality
    • May alter family relationships
    • Adverse psychological effects
      • Survivor guilt
      • Transmitter guilt
      • Depression
      • Anxiety
  • Not appropriate to offer testing for adult onset disorders for prenatal diagnosis or to anyone under age 18

Screening and Management OptionsEdit

  • Screening guidelines
    • Colonoscopy
      • Starting at age 25 or 10 years before age of first colorectal cancer diagnosis
      • Repeat annually
      • Surveillance decreases mortality by 65%, decreases CRC by 62%
      • Promotes early detection, improved survival
    • Endometrial and ovarian cancer
      • Transvaginal ultrasound, CA-125 levels starting at age 25 annually or ten years prior to the youngest age of afflicted family member, whichever comes first.
      • Endometrial biopsy annually starting at age 25 or ten years prior to the youngest age of afflicted family member whichever comes first.
    • Stomach
      • If previous family member affected
      • Upper GI endoscopy every 1-2 years starting at age 25 or ten years prior to the youngest age of afflicted family member whichever comes first.
    • Urinary tract
      • If previous family member affected
      • Ultrasound and urine cytology every 1-2 years starting at age 25 or ten years prior to the youngest age of afflicted family member.
      • Annual Examination of Skin for cancerous growths
  • Prophylactic surgery
  • Subtotal colectomy if cancers are discovered
  • Hysterectomy with oophorectomy following child bearing years

  • Chemoprevention
  • Current multicenter trial recruiting patients with known mutation or high MSI tumors and Amsterdam positive family history
  • Current trial occuring in the UK
  • Not known if chemopreventative therapies are effective for those with Lynch syndrome however prophylactic chemotherapy is prescribed at Stage II and above.

Psychosocial IssuesEdit

  • Motivation for undergoing testing
    • Decision-making about testing, surveillance, and prevention
    • Protect lives
    • Stress level, previous experiences with cancer either within self or other family members
    • Protection of family members
    • Hope and enhanced longevity

  • Reactions to positive, negative, and uninformative results
    • Changes in medical management
    • Initial feeling of being overwhelmed
    • Feelings of relief and/or resolution
    • Notification to family members in order to protect them
  • Family, social support system

ResourcesEdit

  • American Cancer Society
National Headquarters
1599 Clifton Road, N.E.
Atlanta, GA 30329
(800) ACS-2345
  • Hereditary Colorectal Cancer Registry
The Johns Hopkins Hospital
550 North Broadway, Suite 108
Baltimore, MD 21205-2011
(410) 955-3875
:*Lynch Syndrome International
P.O. Box 5456
Vacaville, California
707-689-5089

ReferencesEdit

  • Everett, J. "Hereditary Non-Polyposis Colorectal Cancer." Genetic Counseling and Cancer lecture (2002).
  • "Identifying and Managing Risk for Hereditary Nonpolyposis Colorectal Cancer and Endometrial Cancer (HNPCC)." American Medical Association (2001).
  • "Module 6: Hereditary Colorectal Cancer Syndromes." OncoSep 43-55.
  • "The Johns Hopkins Guide for Patients and Families: Hereditary Nonpolyposis Colorectal Cancer." The Johns Hopkins University (1995).

NotesEdit

The information in this outline was last updated in 2002.


'This material has been imported fom the wikibook "Genetic counseling"[ 'http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.

Heckert GNU white Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1.2 or any later version published by the Free Software Foundation; with no Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts. A copy of the license is included in the section entitled "GNU Free Documentation License."

Ad blocker interference detected!


Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers

Wikia is not accessible if you’ve made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected.

Also on Fandom

Random Wiki