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Familial Cancer
Published in: Familial Cancer 1/2022

01-01-2022 | Colonoscopy | Review

Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome

Author: Hans F. A. Vasen

Published in: Familial Cancer | Issue 1/2022

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Abstract

Lynch syndrome is the most frequent hereditary colorectal cancer (CRC) syndrome, affecting approximately 1 in 300 in the Western population. It is caused by pathogenic variants in the mismatch repair (MMR) genes including MLH1, MSH2 (EPCAM), MSH6 and PMS2, and is associated with high risks of CRC, endometrial cancer and other cancers. In view of these risks, carriers of such variants are encouraged to participate in colonoscopic surveillance programs that are known to substantially improve their prognosis. In the last decade several important studies have been published that provide detailed cancer risk estimates and prognoses based on large numbers of patients. These studies also provided new insights regarding the pathways of carcinogenesis in CRC, which appear to differ depending on the specific MMR gene defect. In this report, we will discuss the implications of these new findings for the development of new surveillance protocols.
Literature
1.
Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG et al (2017) Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomark Prev 26(3):404–412
2.
3.
Dominguez-Valentin M, Sampson JR, Seppala TT, Ten Broeke SW, Plazzer JP, Nakken S et al (2020) Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med 22(1):15–25PubMed
4.
Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM et al (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104(5):1535–1549PubMed
5.
Lynch HT, Watson P, Lanspa SJ, Marcus J, Smyrk T, Fitzgibbons RJ Jr et al (1988) Natural history of colorectal cancer in hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). Dis Colon Rectum 31(6):439–444PubMed
6.
Vasen HF, Nagengast FM, Khan PM (1995) Interval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome). Lancet 345(8958):1183–1184PubMed
7.
Engel C, Rahner N, Schulmann K, Holinski-Feder E, Goecke TO, Schackert HK et al (2010) Efficacy of annual colonoscopic surveillance in individuals with hereditary nonpolyposis colorectal cancer. Clin Gastroenterol Hepatol 8(2):174–182PubMed
8.
Haanstra JF, Kleibeuker JH, Koornstra JJ (2013) Role of new endoscopic techniques in Lynch syndrome. Fam Cancer 12(2):267–272PubMed
9.
Mecklin JP, Jarvinen HJ, Aukee S, Elomaa I, Karjalainen K (1987) Screening for colorectal carcinoma in cancer family syndrome kindreds. Scand J Gastroenterol 22(4):449–453PubMed
10.
Vasen HF, den Hartog Jager FC, Menko FH, Nagengast FM (1989) Screening for hereditary non-polyposis colorectal cancer: a study of 22 kindreds in The Netherlands. Am J Med 86(3):278–281PubMed
11.
Jarvinen HJ, Mecklin JP, Sistonen P (1995) Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 108(5):1405–1411PubMed
12.
Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P et al (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118(5):829–834
13.
Mecklin JP, Aarnio M, Laara E, Kairaluoma MV, Pylvanainen K, Peltomaki P et al (2007) Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome. Gastroenterology 133(4):1093–1098PubMed
14.
Vasen HF, Abdirahman M, Brohet R, Langers AM, Kleibeuker JH, van Kouwen M et al (2010) One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology 138(7):2300–2306PubMed
15.
Stupart DA, Goldberg PA, Algar U, Ramesar R (2009) Surveillance colonoscopy improves survival in a cohort of subjects with a single mismatch repair gene mutation. Colorectal Dis 11(2):126–130PubMed
16.
Newton K, Green K, Lalloo F, Evans DG, Hill J (2015) Colonoscopy screening compliance and outcomes in patients with Lynch syndrome. Colorectal Dis 17(1):38–46PubMed
17.
Stuckless S, Green JS, Morgenstern M, Kennedy C, Green RC, Woods MO et al (2012) Impact of colonoscopic screening in male and female Lynch syndrome carriers with an MSH2 mutation. Clin Genet 82(5):439–445PubMed
18.
19.
Zhao S, Wang S, Pan P, Xia T, Chang X, Yang X et al (2019) Magnitude, risk factors, and factors associated with adenoma miss rate of tandem colonoscopy: a systematic review and meta-analysis. Gastroenterology 156(6):1661–1674PubMed
20.
Latchford A (2020) How should colonoscopy surveillance in Lynch syndrome be performed? Gastroenterology 158(4):818–819PubMed
21.
Haanstra JF, Dekker E, Cats A, Nagengast FM, Hardwick JC, Vanhoutvin SA et al (2019) Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial. Gastrointest Endosc 90(4):624–632PubMed
22.
Rivero-Sanchez L, Arnau-Collell C, Herrero J, Remedios D, Cubiella J, Garcia-Cougil M et al (2020) White-light endoscopy is adequate for Lynch syndrome surveillance in a randomized and noninferiority study. Gastroenterology 158(4):895–904PubMed
23.
Argillander TE, Koornstra JJ, van Kouwen M, Langers AM, Nagengast FM, Vecht J et al (2018) Features of incident colorectal cancer in Lynch syndrome. United Eur Gastroenterol J 6(8):1215–1222
24.
De Jong AE, Morreau H, Van Puijenbroek M, Eilers PH, Wijnen J, Nagengast FM et al (2004) The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology 126(1):42–48PubMed
25.
26.
Love RR (1986) Adenomas are precursor lesions for malignant growth in nonpolyposis hereditary carcinoma of the colon and rectum. Surg Gynecol Obstet 162(1):8–12PubMed
27.
Kloor M, Huth C, Voigt AY, Benner A, Schirmacher P, von Knebel DM et al (2012) Prevalence of mismatch repair-deficient crypt foci in Lynch syndrome: a pathological study. Lancet Oncol 13(6):598–606PubMed
28.
Pedroni M, Sala E, Scarselli A, Borghi F, Menigatti M, Benatti P et al (2001) Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis. Cancer Res 61(3):896–899PubMed
29.
Sekine S, Mori T, Ogawa R, Tanaka M, Yoshida H, Taniguchi H et al (2017) Mismatch repair deficiency commonly precedes adenoma formation in Lynch syndrome-associated colorectal tumorigenesis. Mod Pathol 30(8):1144–1151PubMed
30.
Ahadova A, Gallon R, Gebert J, Ballhausen A, Endris V, Kirchner M et al (2018) Three molecular pathways model colorectal carcinogenesis in Lynch syndrome. Int J Cancer 143(1):139–150PubMed
31.
Mecklin JP, Sipponen P, Jarvinen HJ (1986) Histopathology of colorectal carcinomas and adenomas in cancer family syndrome. Dis Colon Rectum 29(12):849–853PubMed
32.
Rijcken FE, Hollema H, Kleibeuker JH (2002) Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation. Gut 50(3):382–386PubMedPubMedCentral
33.
Ahadova A, von Knebel DM, Blaker H, Kloor M (2016) CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome. Fam Cancer 15(4):579–586PubMed
34.
Miyaki M, Iijima T, Kimura J, Yasuno M, Mori T, Hayashi Y et al (1999) Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer. Cancer Res 59(18):4506–4509PubMed
35.
Johnson V, Volikos E, Halford SE, Eftekhar Sadat ET, Popat S, Talbot I et al (2005) Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome. Gut 54(2):264–267PubMedPubMedCentral
36.
Huels DJ, Ridgway RA, Radulescu S, Leushacke M, Campbell AD, Biswas S et al (2015) E-cadherin can limit the transforming properties of activating beta-catenin mutations. EMBO J 34(18):2321–2333PubMedPubMedCentral
37.
Moller P, Seppala T, Bernstein I, Holinski-Feder E, Sala P, Evans DG et al (2017) Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut 66(3):464–472PubMed
38.
Moller P, Seppala T, Bernstein I, Holinski-Feder E, Sala P, Evans DG et al (2017) Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut 66(9):1657–1664PubMed
39.
Moller P, Seppala TT, Bernstein I, Holinski-Feder E, Sala P, Gareth Evans D et al (2018) Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 67(7):1306–1316PubMed
40.
Seppala T, Pylvanainen K, Evans DG, Jarvinen H, Renkonen-Sinisalo L, Bernstein I et al (2017) Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols: a prospective Lynch syndrome database report. Hered Cancer Clin Pract 15:18PubMedPubMedCentral
41.
Dominguez-Valentin M, Seppala TT, Sampson JR, Macrae F, Winship I, Evans DG et al (2019) Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report. Hered Cancer Clin Pract 17:28PubMedPubMedCentral
42.
Seppala TT, Ahadova A, Dominguez-Valentin M, Macrae F, Evans DG, Therkildsen C et al (2019) Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrome database report. Hered Cancer Clin Pract 17:8PubMedPubMedCentral
43.
ten Broeke SW, Brohet RM, Tops CM, van der Klift HM, Velthuizen ME, Bernstein I et al (2015) Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. J Clin Oncol 33(4):319–325PubMed
44.
Ten Broeke SW, van der Klift HM, Tops CMJ, Aretz S, Bernstein I, Buchanan DD et al (2018) Cancer risks for PMS2-associated Lynch syndrome. J Clin Oncol 36:2961PubMedPubMedCentral
45.
Engel C, Vasen HF, Seppala T, Aretz S, Bigirwamungu-Bargeman M, de Boer SY et al (2018) No difference in colorectal cancer incidence or stage at detection by colonoscopy among 3 countries with different Lynch syndrome surveillance policies. Gastroenterology 155(5):1400–1409PubMed
46.
Engel C, Ahadova A, Seppala TT, Aretz S, Bigirwamungu-Bargeman M, Blaker H et al (2020) Associations of pathogenic variants in MLH1, MSH2, and MSH6 with risk of colorectal adenomas and tumors and with somatic mutations in patients with Lynch syndrome. Gastroenterology 158(5):1326–1333PubMed
47.
Ten Broeke SW, van Bavel TC, Jansen AML, Gomez-Garcia E, Hes FJ, van Hest LP et al (2018) Molecular background of colorectal tumors from patients with Lynch syndrome associated with germline variants in PMS2. Gastroenterology 155(3):844–851PubMed
48.
Schwitalle Y, Kloor M, Eiermann S, Linnebacher M, Kienle P, Knaebel HP et al (2008) Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology 134(4):988–997PubMed
49.
50.
Yurgelun MB, Goel A, Hornick JL, Sen A, Turgeon DK, Ruffin MTT et al (2012) Microsatellite instability and DNA mismatch repair protein deficiency in Lynch syndrome colorectal polyps. Cancer Prev Res (Phila) 5(4):574–582
51.
Walsh MD, Buchanan DD, Pearson SA, Clendenning M, Jenkins MA, Win AK et al (2012) Immunohistochemical testing of conventional adenomas for loss of expression of mismatch repair proteins in Lynch syndrome mutation carriers: a case series from the Australasian site of the colon cancer family registry. Mod Pathol 25(5):722–730PubMedPubMedCentral
52.
Goverde A, Eikenboom EL, Viskil EL, Bruno MJ, Doukas M, Dinjens WNM et al (2020) Yield of Lynch syndrome surveillance for patients with pathogenic variants in DNA mismatch repair genes. Clin Gastroenterol Hepatol 18(5):1112–1120PubMed
53.
Rubenstein JH, Enns R, Heidelbaugh J, Barkun A, Clinical GC (2015) American Gastroenterological Association Institute guideline on the diagnosis and management of Lynch syndrome. Gastroenterology 149(3):777–782PubMed
54.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW et al (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110(2):223–262PubMedPubMedCentral
55.
van Leerdam ME, Roos VH, van Hooft JE, Balaguer F, Dekker E, Kaminski MF et al (2019) Endoscopic management of Lynch syndrome and of familial risk of colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 51(11):1082–1093PubMed
56.
Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE et al (2020) Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 69(3):411–444PubMed
57.
Seppala TT, Latchford A, Negoi I, Sampaio Soares A, Jimenez-Rodriguez R, Sanchez-Guillen L et al (2020) European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. Br J Surg. https://​doi.​org/​10.​1002/​bjs.​11902
58.
Vasen HF, Tomlinson I, Castells A (2015) Clinical management of hereditary colorectal cancer syndromes. Nat Rev Gastroenterol Hepatol 12(2):88–97PubMed
Metadata
Title
Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome
Author
Hans F. A. Vasen
Publication date
01-01-2022
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 1/2022
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-020-00225-x

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