Ewha Med J.  2017 Jan;40(1):29-34. 10.12771/emj.2017.40.1.29.

Hereditary Nonpolyposis Colorectal Cancer

Affiliations
  • 1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. obbyy@hanmail.net

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary colorectal cancer syndrome and accounts for about 5% of colorectal cancer. It is inherited as autosomal dominant type and is caused by germline mutations in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2. Patients with HNPCC are characterized by a high level of microsatellite instability. They commonly develop colorectal cancer at young age and increase risk of extra-colic malignancies, especially endometrial cancer. They also show better oncologic outcomes compared to sporadic colorectal cancer. Several tools are used in diagnosis of HNPCC, including history taking, microsatellite instability test, immunohistochemistry for mismatch repair protein, and gene test. Affected patients and their families should get genetic counseling and regular surveillance for cancers, which can improve their survival rate.

Keyword

Colorectal neoplasms, hereditary nonpolyposis; DNA mismatch repair; Microsatellite instability; Genetic testing

MeSH Terms

Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis*
Diagnosis
DNA Mismatch Repair
Endometrial Neoplasms
Female
Genetic Counseling
Genetic Testing
Germ-Line Mutation
Humans
Immunohistochemistry
Microsatellite Instability
Survival Rate

Figure

  • Fig. 1 Diagnostic approach of hereditary nonpolyposis colorectal cancer. MSI, microsatellite instability; MSI-H, high level of MSI; IHC, immunohistochemistry; MMR, mismatch repair; MSS, microsatellite stable; MSI-L, low level of MSI.


Reference

1. Oh BY, Lee WY, Jung S, Hong HK, Nam DH, Park YA, et al. Correlation between tumor engraftment in patient-derived xenograft models and clinical outcomes in colorectal cancer patients. Oncotarget. 2015; 6:16059–16068.
2. Mork ME, You YN, Ying J, Bannon SA, Lynch PM, Rodriguez-Bigas MA, et al. High prevalence of hereditary cancer syndromes in adolescents and young adults with colorectal cancer. J Clin Oncol. 2015; 33:3544–3549.
3. Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005; 293:1979–1985.
4. Hegde MR, Roa BB. Genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC). Curr Protoc Hum Genet. 2009; Chapter 10:Unit 10.12.
5. Heneghan HM, Martin ST, Winter DC. Segmental vs extended colectomy in the management of hereditary nonpolyposis colorectal cancer: a systematic review and meta-analysis. Colorectal Dis. 2015; 17:382–389.
6. Silva FC, Valentin MD, Ferreira Fde O, Carraro DM, Rossi BM. Mismatch repair genes in Lynch syndrome: a review. Sao Paulo Med J. 2009; 127:46–51.
7. Steinke V, Engel C, Buttner R, Schackert HK, Schmiegel WH, Propping P. Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. Dtsch Arztebl Int. 2013; 110:32–38.
8. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009; 76:1–18.
9. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015; 110:223–262. quiz 263.
10. Edelstein DL, Axilbund J, Baxter M, Hylind LM, Romans K, Griffin CA, et al. Rapid development of colorectal neoplasia in patients with Lynch syndrome. Clin Gastroenterol Hepatol. 2011; 9:340–343.
11. Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010; 138:2044–2058.
12. Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. Milestones of Lynch syndrome: 1895-2015. Nat Rev Cancer. 2015; 15:181–194.
13. Fu L, Sheng JQ, Li XO, Jin P, Mu H, Han M, et al. Mismatch repair gene mutation analysis and colonoscopy surveillance in Chinese Lynch syndrome families. Cell Oncol (Dordr). 2013; 36:225–231.
14. Kloor M, Staffa L, Ahadova A, von Knebel Doeberitz M. Clinical significance of microsatellite instability in colorectal cancer. Langenbecks Arch Surg. 2014; 399:23–31.
15. Imai K, Yamamoto H. Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis. 2008; 29:673–680.
16. Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007; 21:2525–2538.
17. Peltomaki P, Vasen H. Mutations associated with HNPCC predisposition: update of ICG-HNPCC/INSiGHT mutation database. Dis Markers. 2004; 20:269–276.
18. Plaschke J, Engel C, Kruger S, Holinski-Feder E, Pagenstecher C, Mangold E, et al. 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. 2004; 22:4486–4494.
19. Kovacs ME, Papp J, Szentirmay Z, Otto S, Olah E. Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome. Hum Mutat. 2009; 30:197–203.
20. Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3’ exons of TACSTD1. Nat Genet. 2009; 41:112–117.
21. Ligtenberg MJ, Kuiper RP, Geurts van Kessel A, Hoogerbrugge N. EPCAM deletion carriers constitute a unique subgroup of Lynch syndrome patients. Fam Cancer. 2013; 12:169–174.
22. Niessen RC, Hofstra RM, Westers H, Ligtenberg MJ, Kooi K, Jager PO, et al. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome. Genes Chromosomes Cancer. 2009; 48:737–744.
23. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004; 96:261–268.
24. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999; 116:1453–1456.
25. Gelsomino F, Barbolini M, Spallanzani A, Pugliese G, Cascinu S. The evolving role of microsatellite instability in colorectal cancer: a review. Cancer Treat Rev. 2016; 51:19–26.
26. Vilar E, Gruber SB. Microsatellite instability in colorectal cancer-the stable evidence. Nat Rev Clin Oncol. 2010; 7:153–162.
27. Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, et al. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 2006; 8:305–311.
28. Pagin A, Zerimech F, Leclerc J, Wacrenier A, Lejeune S, Descarpentries C, et al. Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours. Br J Cancer. 2013; 108:2079–2087.
29. Xicola RM, Llor X, Pons E, Castells A, Alenda C, Pinol V, et al. Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst. 2007; 99:244–252.
30. Hatch SB, Lightfoot HM Jr, Garwacki CP, Moore DT, Calvo BF, Woosley JT, et al. Microsatellite instability testing in colorectal carcinoma: choice of markers affects sensitivity of detection of mismatch repair-deficient tumors. Clin Cancer Res. 2005; 11:2180–2187.
31. Kawakami H, Zaanan A, Sinicrope FA. Microsatellite instability testing and its role in the management of colorectal cancer. Curr Treat Options Oncol. 2015; 16:30.
32. Yamamoto H, Imai K. Microsatellite instability: an update. Arch Toxicol. 2015; 89:899–921.
33. Brooks J, Ding J, Simon-Sanchez J, Paisan-Ruiz C, Singleton AB, Scholz SW. Parkin and PINK1 mutations in early-onset Parkinson's disease: comprehensive screening in publicly available cases and control. J Med Genet. 2009; 46:375–381.
34. Rubenstein JH, Enns R, Heidelbaugh J, Barkun A. Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the diagnosis and management of Lynch syndrome. Gastroenterology. 2015; 149:777–782. quiz e16-e17.
35. DA Silva FC, Wernhoff P, Dominguez-Barrera C, Dominguez-Valentin M. Update on hereditary colorectal cancer. Anticancer Res. 2016; 36:4399–4405.
36. Win AK, Parry S, Parry B, Kalady MF, Macrae FA, Ahnen DJ, et al. Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers. Ann Surg Oncol. 2013; 20:1829–1836.
37. de Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, Menko FH, Taal BG, Kleibeuker JH, et al. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum. 2002; 45:1588–1594.
38. Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, et al. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut. 2011; 60:950–957.
39. Baucom RB, Wise PE. Endoscopic and surgical management of hereditary nonpolyposis colorectal cancer. Clin Colon Rectal Surg. 2012; 25:90–96.
40. Schmeler KM, Lynch HT, Chen LM, Munsell MF, Soliman PT, Clark MB, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006; 354:261–269.
41. Chen LM, Yang KY, Little SE, Cheung MK, Caughey AB. Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families. Obstet Gynecol. 2007; 110:18–25.
42. Kehoe SM, Kauff ND. Screening and prevention of hereditary gynecologic cancers. Semin Oncol. 2007; 34:406–410.
43. Yacoub G, Nagalla S, Aklilu M. Oncologic management of hereditary colorectal cancer. Clin Colon Rectal Surg. 2012; 25:118–122.
Full Text Links
  • EMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr