Abstract
Introduction
Lynch syndrome families have a substantial risk of developing colorectal cancer (CRC). The recommended surveillance protocol includes colonoscopy every 2 years from age 20–25 years. It is yet unknown whether annual screening of patients aged 40–60 years is more effective than bi-annual screening, whether patients who had an adenoma removed should be re-examined after a year and whether surveillance of second-degree relatives is indicated. The aim of this study was to address these issues.
Methods
All carriers of a mismatch repair gene mutation who participated in the surveillance program were selected from the Dutch Lynch syndrome registry. The results of colonoscopy were prospectively collected.
Results
A total of 666 mutation carriers were identified in 110 families. Fourty-one CRCs were detected during endoscopic follow-up, of which 34 (83%) were diagnosed between age 40 and 60 years. In five of 34 patients, CRC was diagnosed within 1 year after colonoscopy, eight cancers were diagnosed between 1 and 2 years and the remaining tumors more than 2 years after colonoscopy. All eight CRCs detected between 1 and 2 years were at local stage.
At least one adenoma was diagnosed at 141 examinations. The risk of developing CRC during follow-up in carriers with an adenoma was similar as in carriers without an adenoma at the previous colonoscopy. 280 parent–child couples with at least one Lynch syndrome-related carcinoma were identified in 110 families. In only 19 (6.8%) of these couples, CRC developed earlier in the child than an Lynch syndrome-associated cancer in the parent.
Conclusion
The current surveillance protocol, i.e., bi-annual colonoscopy in first-degree relatives independent of age and endoscopic findings, appears to be appropriate.
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Abbreviations
- HNPCC:
-
Hereditary NonPolyposis Colorectal Cancer
- MMR:
-
MisMatch Repair
- CRC:
-
Colorectal Cancer
References
Mecklin JP (1987) Frequency of hereditary colorectal carcinoma. Gastroenterology 93(5):1021–1025
Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK et al (1994) Mutation in the DNA mismatch repair gene homologue HMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368(6468):258–261
Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA et al (1994) Mutation of a MutL homolog in hereditary colon cancer. Science 263(5153):1625–1629
Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J et al (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75(5):1027–1038
Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R et al (1993) Mutations of a MutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75(6):1215–1225
Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260(5109):812–816
Akiyama Y, Sato H, Yamada T, Nagasaki H, Tsuchiya A, Abe R et al (1997) Germ-line mutation of the HMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Res 57(18):3920–3923
Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M et al (1997) Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet 17(3):271–272
Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, De La Chapelle A et al (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81(2):214–218
Vasen HF, Wijnen JT, Menko FH, Kleibeuker JH, Taal BG, Griffioen G et al (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110(4):1020–1027
Mecklin JP, Jarvinen HJ (1991) Tumor spectrum in cancer family syndrome (Hereditary Nonpolyposis Colorectal Cancer). Cancer 68(5):1109–1112
Vasen HF, Offerhaus GJ, Hartog Jager FC, Menko FH, Nagengast FM, Griffioen G et al (1990) The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 Kindreds in the Netherlands. Int J Cancer 46(1):31–34
Watson P, Lynch HT (1993) Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 71(3):677–685
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
Vasen HF, Nagengast FM, Khan PM (1995) Interval cancers in hereditary non-polyposis colorectal cancer (Lynch Syndrome). Lancet 345(8958):1183–1184
Ahlquist DA (1995) Aggressive polyps in hereditary nonpolyposis colorectal cancer: targets for screening. Gastroenterology 108(5):1590–1592
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):42–48
Jass JR, Stewart SM, Stewart J, Lane MR (1994) Hereditary non-polyposis colorectal cancer – morphologies, genes and mutations. Mutat Res 310(1):125–133
Weber T (1996) Clinical surveillance recommendations adopted for HNPCC
de Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, Menko FH, Taal BG, Kleibeuker et al (2002) Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum 45(12):1588–1594
Rex DK, Johnson DA, Lieberman DA, Burt RW, Sonnenberg A (2000) Colorectal Cancer Prevention 2000: screening recommendations of the American College of gastroenterology. American College of gastroenterology. Am J Gastroenterol 95(4):868–877
Vasen HF, 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):278–281
Wijnen JT, Vasen HF, Khan PM, Zwinderman AH, van der Klift H, Mulder A et al (1998) Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med 339(8):511–518
Wijnen J, de Leeuw W, Vasen H, van der Klift H, Moller P, Stormorken A et al (1999) Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet 23(2):142–144
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de Jong, A.E., Nagengast, F.M., Kleibeuker, J.H. et al. What is the appropriate screening protocol in Lynch syndrome?. Familial Cancer 5, 373–378 (2006). https://doi.org/10.1007/s10689-006-0008-6
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DOI: https://doi.org/10.1007/s10689-006-0008-6