Abstract
Lynch syndrome (LS) is caused by a germline mutations in DNA mismatch repair genes and is a dominantly inherited syndrome, responsible for 2–5% of all colorectal cancer (CRC) cases. Mutation carriers have a 60–85% risk of developing CRC. With the increasing use of genetic predisposition testing, patients and health care providers must decide on cancer risk-reduction strategies. The cancers observed in families with LS are diagnosed at an unusually early age and may be multiple. The decision about which surgery is suitable should be made on the basis of patient factors and preferences, with special emphasis on age, comorbidity, sphincteric function, and the ability of the patient to cope with intensive surveillance. Colectomy decreases the risk of second CRC significantly. The estimated lifetime risk for endometrial adenocarcinoma is 40–60% in women with LS, and the mean age at diagnosis is around 50 years. This risk equals or exceeds the risk of CRC. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear. Patients who are gene mutation carriers should receive counseling about colectomy, and if women, prophylactic hysterectomy and bilateral oophorectomy.
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Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932
Aaltonen LA, Salovaara R, Kristo P et al (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487
Percesepe A, Borghi F, Menigatti M et al (2001) Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective, population-based study. J Clin Oncol 19:3944–3950
Rouprêt M, Yates DR, Comperat E, Cussenot O (2008) Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (lynch syndrome) tumor spectrum. Eur Urol 54:1226–1236
Soravia C, van der Klift H, Bründler MA et al (2003) Prostate cancer is part of the hereditary non-polyposis colorectal cancer (HNPCC) tumor spectrum. Am J Med Genet A 121A:159–162
Risinger JI, Barrett JC, Watson P, Lynch HT, Boyd J (1996) Molecular genetic evidence of the occurrence of breast cancer as an integral tumor in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. Cancer 77:1836–1843
Medina Arana V, Barrios del Pino Y, García-Castro C, González-Aguilera JJ, Fernández-Peralta A, González-Hermoso F (2002) Highly aggressive leiomyosarcoma associated with Lynch II syndrome. Ann Oncol 13:807–808
Huang RL, Chao CF, Ding DC et al (2004) Multiple epithelial and nonepithelial tumors in hereditary nonpolyposis colorectal cancer:characterization of germline and somatic mutations of the MHS2 gene and heterogeneity of replication error phenotypes. Cancer Genet Cytogenet 153:108–114
Salovaara R, Loukola A, Kristo P et al (2000) Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J Clin Oncol 18:2193–2200
Molatore S, Ranzani GN (2004) Genetics of colorectal polyps. Tech Coloproctol 2:S240–S242
Dietmaier W, Wallinger S, Bocker T, Kullmann F, Fishel R, Ruschoff J (1997) Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 57:4749–4756
Bronner CE, Baker SM, Morrison PT et al (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colorectal cancer. Nature 368:258–261
Leach FS, Nicolaides NC, Papadopoulos N et al (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225
Nicolaides NC, Papadopoulos N, Liu B et al (1994) Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371:75–80
Umar A, Boyer JC, Thomas DC et al (1994) Defective mismatch repair in extracts of colorectal and endometrial cancer cell lines exhibiting microsatellite instability. J Biol Chem 269:14367–14370
Menigatti M, Di Gregorio C, Borghi F et al (2001) Methylation pattern of different regions of the MLH1 promoter and silencing of gene expression in hereditary and sporadic colorectal cancer. Genes Chromosomes Cancer 31:357–361
Cunningham JM, Christensen ER, Tester DJ et al (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58:3455–3460
Kastrinos F, Stoffel EM, Balmana J, Steyerberg EW, Mercado R, Syngal S (2008) Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1, 914 individuals undergoing clinical genetic testing in the United States. Cancer Epidemiol Biomarkers Prev 17:2044–2051
Kruse R, Rütten A, Lamberti C et al (1998) Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria. Am J Hum Genet 63:63–70
Watson P, Vasen HF, Mecklin JP et al (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123:444–449
Plaschke J, Engel C, Krüger S et al (2004) Lower incidence of colorectal cancer and later age of disease onset in 27 families with pathogenic MSH6 germline mutations compared with families with MLH1 or MSH2 mutations: the German Hereditary Nonpolyposis Colorectal Cancer Consortium. J Clin Oncol 22:4486–4494
Senter L, Clendenning M, Sotamaa K et al (2008) The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 135:419–428
Vasen HFA, Mecklin JP, Khan PM, Lynch HT (1991) The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34:424–425
Vasen HFA, Watson P, Mecklin JP, Lynch HT (1999) ICG-HNPCC. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 116:1453–1456
Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268
Wahlberg SS, Schmeits J, Thomas G et al (2002) Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 62:3485–3492
Aktan-Collan K, Mecklin JP, Järvinen H et al (2000) Predictive genetic testing for hereditary non-polyposis colorectal cancer: uptake and long-term satisfaction. Int J Cancer 89:44–50
Lindor NM, Rabe K, Petersen GM et al (2005) Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency:familial colorectal cancer type x JAMA 293:1979–1985
Vasen HFA, Wijnen JT, Menko FH et al (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:1020–1027
Love RR (1986) Adenomas are the precursor lesions for malignant growth in nonpolyposis hereditary carcinoma of the colon and rectum. Surg Gynecol Obstet 162:8–12
Mecklin JP, Sipponen P, Jarvinen HJ (1986) Histopathology of colorectal carcinomas and adenomas in cancer family syndrome. Dis Colon Rectum 29:849–853
Jarvinen HJ, Mecklin JP, Sistonen P (1995) Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 108:1405–1411
Jarvinen HJ, Aarnio M, Mustonen H et al (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118:829–834
de Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G et al (2002) Surveillance for hereditary nonpolyposis colorectal cancer. Dis Colon Rectum 45:1588–1594
Lindor NM, Petersen GM, Hadley DW et al (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296:1507–1517
Dove-Edwin I, Sasieni P, Adams J, Thomas HJ (2005) Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer. BMJ 331:1047
Mecklin JP, Aarnio M, Läärä E et al (2007) Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome. Gastroenterology 133:1093–1098
Tominaga K, Nakanishi Y, Nimura S, Yokimura K, Sakai Y, Shimoda T (2005) Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Dis Colon Rectum 48:92–100
Ueno H, Mochizuki H, Hashiguchi Y et al (2004) Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 127:385–394
Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD (1985) Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology 89:328–336
Winawer S, Fletcher R, Rex D, Gastrointestinal Consortium Panel et al (2003) Colorectal cancer screening and surveillance: clinical guidelines and rationale-update based on new evidence. Gastroenterology 124:544–560
van Rijn JC, Reitsma JB, Stoker J, Bossuyt PM, van Deventer SJ, Dekker E (2006) Polyp miss rate determined by tandem colonoscopy: a systematic review. Am J Gastroenterol 101:343–350
Waye JD, Kahn O, Auerbach ME (1996) Complications of colonoscopy and flexible sigmoidoscopy. Gastrointest Endosc Clin N Am 6:343–377
Nicholson FB, Barro JL, Atkin W et al (2005) Review article: population screening for colorectal cancer. Aliment Pharmacol Ther 22:1069–1077
Rabeneck L, Paszat LF, Hilsden RJ et al (2008) Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice. Gastroenterology 135:1899–1906
Taku K, Sano Y, Fu KI et al (2007) Iatrogenic perforation associated with therapeutic colonoscopy: a multicenter study in Japan. J Gastroenterol Hepatol 22:1409–1414
Repici A, Tricerri R (2004) Endoscopic polypectomy: techniques, complications and follow-up. Tech Coloproctol 8:S283–S290
Levin TR, Zhao W, Conell C et al (2006) Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med 145:880–886
Hadley DW, Jenkins JF, Dimond E, de Carvalho M, Kirsch I, Palmer CG (2004) Colon cancer screening practices after genetic counseling and testing for hereditary nonpolyposis colorectal cancer. J Clin Oncol 22:39–44
Bleiker EM, Menko FH, Taal BG et al (2005) Screening behavior of individuals at high risk for colorectal cancer. Gastroenterology 128:280–287
Syngal S, Weeks JC, Schrag D, Garber JE, Kuntz KM (1998) Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations. Ann Intern Med 129:787–796
de Vos tot Nederveen Cappel WH, Buskens E, van Duijvendijk P et al (2003) Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect. Gut 52:1752–1755
Natarajan N, Watson P, Silva-Lopez E, Lynch HT (2010) Comparison of extended colectomy and limited resection in patients with Lynch syndrome. Dis Colon Rectum 53:77–82
Rodriguez-Bigas MA, Vasen HF, Pekka-Mecklin J et al (1997) International Collaborative Group on HNPCC. Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy. Ann Surg 225:202–207
Meyer LA, Broaddus RR, Lu KH (2009) Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control 16:14–22
Aarnio M, Sankila R, Pukkala E et al (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81:214–218
Aarnio M, Mecklin JP, Aaltonen LA, Nyström-Lahti M, Järvinen HJ (1995) Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 64:430–433
Offit K, Kauff ND (2006) Reducing the risk of gynecologic cancer in the Lynch syndrome. N Engl J Med 354:293–295
Dunlop MG, Farrington SM, Carothers AD et al (1997) Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 6:105–110
Schmeler KM, Lynch HT, Chen LM et al (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354:261–269
Vasen HF, Stormorken A, Menko FH et al (2001) MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol 19:4074–4080
Watson P, Bützow R, Lynch HT et al (2001) The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 82:223–228
Lynch HT, Casey MJ (2007) Prophylactic surgery prevents endometrial and ovarian cancer in Lynch syndrome. Nat Clin Pract Oncol 4:672–673
Renkonen-Sinisalo L, Bützow R, Leminen A, Lehtovita P, Mecklin JP, Järvinen HJ (2007) Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome. Int J Cancer 120:821–824
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Celentano, V., Luglio, G., Antonelli, G. et al. Prophylactic surgery in Lynch syndrome. Tech Coloproctol 15, 129–134 (2011). https://doi.org/10.1007/s10151-010-0666-0
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DOI: https://doi.org/10.1007/s10151-010-0666-0