Hereditary Colorectal Cancer Follow-up

  • Author: Juan Carlos Munoz, MD; Chief Editor: Julian Katz, MD   more...
 
Updated: Oct 31, 2011
 

Patient Education

Intestinal Multiple Polyposis and Colorectal Cancer (IMPACC)

A national network founded in 1986. Support network to help patients and families dealing with familial polyposis and hereditary colon cancer. Provides information and referrals, encourages research, and educates professionals and public. Phone support network, correspondence, and literature.

IMPACC

c/o Ann Fagan

PO Box 11

Conyngham, PA 18219

Phone: 570-788-1818 (day);570-788-3712 (eve)

Fax: 570-788-4046

E-mail: impacc@epix.net or pjfagan@epix.net

(verified as of 2/25/2009)

The American Cancer Society provides assistance to those with cancer. Check the telephone directory for your local chapter.

American Cancer Society

National Home Office

250 Williams St NW

Atlanta, GA 30303-1002

Phone: 404-320-3333

Website: http://www.cancer.org/

Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) was established in 1995 "to improve understanding of the basic science of inherited colorectal cancer and the clinical management of affected families." The CGA-ICC's focus is to provides education to professionals and patients, access to clinical and chemoprevention trials, resources for developing new genetic registers, and a forum for collaborative research.

Collaborative Group of the Americas

Dr. James Church

Cleveland Clinic

Department of Colorectal Surgery

Digestive Disease Institute

9500 Euclid Avenue, Desk A30

Cleveland OH 44195, USA

Phone: 216-444-9052

Website: http://www.cgaicc.com/

Johns Hopkins Hereditary Colorectal Cancer Website provides education and information about hereditary colorectal cancer.

Johns Hopkins Hereditary Colorectal Cancer Website

E-mail: hopkinsgi@jhmi.edu

Website: http://hopkins-gi.nts.jhu.edu/

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Prognosis

The 5-year survival rate among patients with hereditary nonpolyposis colorectal cancer (HNPCC) is estimated to be approximately 60%, compared with 40-50% for sporadic cases. Colorectal tumors that are MSI-positive have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrated, and a poorly differentiated, mucinous or signet ring appearance.[51] Investigators have found that MSI-positive tumors are associated with improved survival rates.[24, 52, 53]

When compared based on stage, patients with colorectal cancer from families with a history of HNPCC have a better prognosis than patients with colorectal cancer in the general population, which may be explained by immunologic factors. Immunologic studies in mice with colon cancer have demonstrated that tumors influence host immune response by altering host T-cell receptors.[54] However, the defective T-cell response was observed only in animals with long-standing tumors, implying that rapid tumor growth, as seen in HNPCC, may preserve immune response.[54] This hypothesis merits further investigation.

The best evidence that colonoscopic screening is beneficial for preventing colon cancer in patients with HNPCC has come from observational studies of 22 HNPCC families that were followed for 15 years.[55, 56] One hundred and thirty-three family members were voluntarily screened every 3 years, and 119 declined colonoscopic surveillance during the study period.

Colorectal cancer was reduced by 62% in the screened group versus the unscreened group. The reduction was ascribed to polypectomies in the intervention group. No colorectal cancer-related deaths occurred in the group that underwent regular colonoscopic screening compared with a 36% colorectal cancer-related mortality rate in the unscreened group.

Colon cancers that occur in patients with HNPCC are believed to arise from adenomas; however, these adenomatous polyps likely have a shortened adenoma-carcinoma progression sequence compared with the general population. Thus, for a known MLH1 or MSH2 germline mutation carrier, full colonoscopy every 1-2 years beginning at ages 20-25 years or 5 years before the first diagnosed colorectal cancer in the family is recommended. After the age of 35-40 years, colonoscopy should be performed annually.

The implementation of colorectal tumor testing to identify families with HNPCC or Lynch syndrome could yield substantial benefits at acceptable cost, particularly in females with a mutation associated with HNPCC or Lynch syndrome who begin regular screening and have-reducing surgery. The cost-effectiveness of such testing depends on a particular rate among relatives at risk for HNPCC or Lynch syndrome.[11]

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Summary

Hereditary nonpolyposis colorectal cancer is an autosomal-dominant syndrome that accounts for 2-5% of all colorectal carcinomas.

Colorectal cancer in patients with HNPCC presents at an earlier age than in the general population and is characterized by an increased risk of other cancers, such as endometrial cancer and, to a lesser extent, cancers of the ovary, stomach, small intestine, hepatobiliary tract, pancreas, upper urinary tract, prostrate, brain, and skin. The tumor testing (ie, IHC, MSI, germline testing, and BRAF mutation testing), screening, and prophylactic surgery all help to reduce death of patient with HNPCC or Lynch syndrome.

The benefits of all strategies primarily affect relatives with a mutation associated with HNPCC or Lynch syndrome.

The widespread implementation of colorectal tumor testing help to identify families with HNPCC or Lynch syndrome.

Colorectal tumor testing could yield substantial benefits at acceptable cost. Particularly in females with a mutation associated with HNPCC or Lynch syndrome who begin regular screening and have reducing surgery. The cost-effectiveness of such testing depends on a particular rate among relative at risk for HNPCC or Lynch syndrome.

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Contributor Information and Disclosures
Author

Juan Carlos Munoz, MD  Associate Professor of Medicine and Director of the Endoscopy Unit, Division of Gastroenterology, University of Florida College of Medicine at Jacksonville

Juan Carlos Munoz, MD is a member of the following medical societies: American College of Physicians, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Coauthor(s)

Louis R Lambiase, MD, MHA  Professor of Medicine, University of Tennessee College of Medicine Chattanooga; Chief, Division of Gastroenterology, University of Tennessee Chattanooga Unit; Assistant Dean for Clinical Affairs, University of Tennessee College of Medicine Chattanooga

Louis R Lambiase, MD, MHA is a member of the following medical societies: American Gastroenterological Association, American Pancreatic Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Simmy Bank, MD  Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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Example of an autosomal dominant pedigree.
Diagnostic approach for patients with colorectal tumors.
Table 1. Seven different genes are known to be associated with HNPCC, and all of them are involved with DNA mismatch repair, identified with the frequencies below.
Mismatch Excision Repaired MMRChromosome LocationFrequency of HNPCC Cases
MSH22p1645-50%
MLH13p22.3/A>20%
MSH62p1610%
PMS27p22.11%
PMS12q32.2Rare
MSH35q14.1Rare
EXO11q43Rare
Other genes not yet discovered20-25%
Table 2. Incidence of different types of cancers between individuals with Lynch syndrome and those in the general population.
Type of CancerGeneral Population Risk (by age 70 y)Lynch Syndrome Risk (by age 70 y)
Endometrial1.5%30-40%
Ovarian1%9-12%
Upper Urinary TractLess than 1%4-10%
StomachLess than 1%13% (higher in Asians)
Small BowelLess than 1%1-3%
BrainLess than 1%1-4%
Biliary TractLess than 1%1-5%
Table 3. IHC staining findings.
MMR MutationsProtein Staining
MLH1MSH2MSH6PMS2
MLH1-++-
MSH2+--+
MSH6++-+
PMS2+++-
Table 4. Netherlands surveillance protocol for carriers of an MMR-gene mutation.
SurveillanceMLH1, MSH2, MSH6 (males)MSHG (females)
ColonColonoscopy, every 1-2 years, starting at age 20-25 yearsColonoscopy, every 1-2 years, starting at age 30 years
EndometriumUltrasonography and CA-125, every 1-2 years, starting at age 30-35 yearsUltrasonography and CA-125, every 1-2 years, starting at age 30-35 years; consider hysterectomy after age 50 years
Upper Urinary TractUrine cytology analysis, every 1-2 years, starting at age 30-35 years, if it occurs 2 or more times in a familyUrine cytology analysis, every 1-2 years, starting at age 30-35 years, if it occurs 2 or more times in a family
StomachGastroscopy every 1-2 years, starting at age 30-35 years, if it occurs 2 or more times in a familyGastroscopy every 1-2 years, starting at age 30-35 years, if it occurs 2 or more times in a family
Table 5. Dukes classification.
StageTumorNodeMetastasisDukes
Stage 1T1N0M0Dukes A
T2N0M0
Stage IIT3N0M0Dukes B
T4N0M0
Stage IIIAny TN1M0Dukes C
Any TN2, N3Mo
Stage IVAny TAny NM1Dukes D
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