Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management
- Peter A L Bonis, MD
Peter A L Bonis, MD
- Chief Medical Officer — UpToDate
- Deputy Editor — Gastroenterology/Hepatology
- Adjunct Professor of Medicine
- Tufts University School of Medicine
- Dennis J Ahnen, MD
Dennis J Ahnen, MD
- Director, Genetics Clinic
- Gastroenterology of the Rockies
- Lisen Axell, MS, CGC
Lisen Axell, MS, CGC
- Genetic Counselor
- University of Colorado Comprehensive Cancer Center
- Section Editors
- J Thomas Lamont, MD
J Thomas Lamont, MD
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — Anorectal Disorders and Misc. Lower GI Disease
- Section Editor — Nutrition, Malabsorption, and Misc. Upper GI Disease
- Professor of Medicine
- Harvard Medical School
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
Lynch syndrome is an autosomal dominant disorder characterized by an increased risk of colorectal cancer (CRC) and endometrial cancer as well as a risk of several other malignancies . This topic review will discuss the recommendations for screening and surveillance of individuals with Lynch syndrome and their families. Guidelines for cancer screening in patients diagnosed with Lynch syndrome have been proposed by several groups and are largely based on expert opinion and limited observational data [2-17]. Our recommendations are largely consistent with the United States Multi-Society Task Force on Colorectal Cancer and the American College of Gastroenterology [4,17].
The clinical manifestations and diagnosis of Lynch syndrome, the management of patients and families with other hereditary colon cancer syndromes, and screening strategies in patients with a family history of CRC or polyps who are not known to have one of the above conditions are discussed elsewhere. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Familial adenomatous polyposis: Screening and management of patients and families" and "Juvenile polyposis syndrome" and "Screening for colorectal cancer in patients with a family history of colorectal cancer".)
●Hereditary nonpolyposis colorectal cancer (HNPCC) refers to patients and/or families who fulfill Amsterdam clinical criteria for Lynch syndrome (table 1). (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Amsterdam criteria'.)
●Lynch syndrome refers to patients and families with a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene.
Individuals with Lynch syndrome have an increased risk of colorectal and endometrial cancer . Other sites of cancer include the ovary, stomach, small bowel, hepatobiliary system, renal pelvis, ureter, brain, and skin. There may also be an increased risk of breast, prostate, and pancreatic cancer in individuals with Lynch syndrome. Among individuals with Lynch syndrome, the lifetime cancer risk and therefore some screening recommendations vary by genotype (table 2). (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Genotype phenotype correlation'.)
- Lindor NM, Greene MH. The concise handbook of family cancer syndromes. Mayo Familial Cancer Program. J Natl Cancer Inst 1998; 90:1039.
- Burke W, Petersen G, Lynch P, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 1997; 277:915.
- Dunlop MG, British Society for Gastroenterology, Association of Coloproctology for Great Britain and Ireland. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut 2002; 51 Suppl 5:V21.
- Giardiello FM, Allen JI, Axilbund JE, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Dis Colon Rectum 2014; 57:1025.
- Vasen HF, Blanco I, Aktan-Collan K, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 2013; 62:812.
- Engel C, Rahner N, Schulmann K, et al. Efficacy of annual colonoscopic surveillance in individuals with hereditary nonpolyposis colorectal cancer. Clin Gastroenterol Hepatol 2010; 8:174.
- de Jong AE, Hendriks YM, Kleibeuker JH, et al. Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology 2006; 130:665.
- Järvinen HJ, Aarnio M, Mustonen H, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000; 118:829.
- Lynch P. If aggressive surveillance in hereditary nonpolyposis colorectal cancer is now state of the art, are there any challenges left? Gastroenterology 2000; 118:969.
- Schulmann K, Brasch FE, Kunstmann E, et al. HNPCC-associated small bowel cancer: clinical and molecular characteristics. Gastroenterology 2005; 128:590.
- Brown GJ, St John DJ, Macrae FA, Aittomäki K. Cancer risk in young women at risk of hereditary nonpolyposis colorectal cancer: implications for gynecologic surveillance. Gynecol Oncol 2001; 80:346.
- Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 2006; 354:261.
- Dove-Edwin I, Boks D, Goff S, et al. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 2002; 94:1708.
- Mecklin JP, Aarnio M, Läärä E, et al. Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome. Gastroenterology 2007; 133:1093.
- Stoffel EM, Mangu PB, Gruber SB, et al. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol 2015; 33:209.
- Balmaña J, Balaguer F, Cervantes A, et al. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2013; 24 Suppl 6:vi73.
- Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110:223.
- Syngal S, Weeks JC, Schrag D, et al. Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations. Ann Intern Med 1998; 129:787.
- Vasen HF, Abdirahman M, Brohet R, et al. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology 2010; 138:2300.
- de Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, et al. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum 2002; 45:1588.
- Renkonen-Sinisalo L, Sipponen P, Aarnio M, et al. No support for endoscopic surveillance for gastric cancer in hereditary non-polyposis colorectal cancer. Scand J Gastroenterol 2002; 37:574.
- ten Kate GL, Kleibeuker JH, Nagengast FM, et al. Is surveillance of the small bowel indicated for Lynch syndrome families? Gut 2007; 56:1198.
- Saurin JC, Pilleul F, Soussan EB, et al. Small-bowel capsule endoscopy diagnoses early and advanced neoplasms in asymptomatic patients with Lynch syndrome. Endoscopy 2010; 42:1057.
- Myrhøj T, Andersen MB, Bernstein I. Screening for urinary tract cancer with urine cytology in Lynch syndrome and familial colorectal cancer. Fam Cancer 2008; 7:303.
- South CD, Hampel H, Comeras I, et al. The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst 2008; 100:277.
- Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 2013; 62:339.
- Lindor NM, Petersen GM, Hadley DW, et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 2006; 296:1507.
- Kalady MF, McGannon E, Vogel JD, et al. Risk of colorectal adenoma and carcinoma after colectomy for colorectal cancer in patients meeting Amsterdam criteria. Ann Surg 2010; 252:507.
- Win AK, Parry S, Parry B, et al. Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers. Ann Surg Oncol 2013; 20:1829.
- Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993; 260:816.
- Lothe RA, Peltomäki P, Meling GI, et al. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 1993; 53:5849.
- Gryfe R, Kim H, Hsieh ET, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000; 342:69.
- Sankila R, Aaltonen LA, Järvinen HJ, Mecklin JP. Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 1996; 110:682.
- Watanabe T, Wu TT, Catalano PJ, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 2001; 344:1196.
- Kohonen-Corish MR, Daniel JJ, Chan C, et al. Low microsatellite instability is associated with poor prognosis in stage C colon cancer. J Clin Oncol 2005; 23:2318.
- Lanza G, Gafà R, Santini A, et al. Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol 2006; 24:2359.
- Malesci A, Laghi L, Bianchi P, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res 2007; 13:3831.
- Hutchins G, Southward K, Handley K, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011; 29:1261.
- Sinicrope FA, Mahoney MR, Smyrk TC, et al. Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol 2013; 31:3664.
- Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 2011; 378:2081.
- Burn J, Bishop DT, Mecklin JP, et al. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. N Engl J Med 2008; 359:2567.
- CANCER SCREENING
- Candidates for screening for Lynch syndrome related cancers
- Colorectal cancer
- Endometrial and ovarian cancer
- Gastric cancer
- Small intestinal cancer
- Urinary tract cancer
- Skin cancer
- Pancreatic cancer
- Other cancers
- MANAGEMENT OF COLORECTAL CANCER
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS