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APC, MYH, and the Correlation Genotype-Phenotype in Colorectal Polyposis

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Familial adenomatous polyposis (FAP) has been divided into two entities: classical (CFAP) and attenuated (AFAP). With the discovery of MYH associated polyposis (MAP) syndrome, the clinical differences have become unclear. The aim of our study was to investigate patients with polyposis treated in our institution for a correlation between genotype and phenotype.

Methods

Between 1978 and 2007, 515 patients were followed. Four groups were identified: AFAP, CFAP, MAP, and no-mutation patients. Clinical, surgical, histological, and genetic data of patients were collected and compared. Two ranges of mutations responsible for AFAP were used.

Results

Patient breakdown was CFAP patients (n = 322/294), AFAP patients (n = 13/41), MYH patients (n = 17) and no-mut patients (n = 32). Patients not tested for APC mutation (n = 131) were excluded. Genotype/phenotype evaluation showed no difference in the number or location of polyps, age at colectomy, presence of cancer, or duodenal polyps. Major differences were found for MYH patients: later age at diagnosis, more cancers, fewer polyps, and more located in the right part of the colon. For phenotype/genotype correlation, patients aged more than 35 years at the time of colectomy and with fewer than 100 polyps had significantly more mutation found on MYH.

Conclusions

This two-way analysis did not show any correlation that might help to identify a subgroup of patients with APC mutation that may be considered attenuated. It is more likely that the MAP syndrome is the real AFAP.

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References

  1. Bouvier AM, Remontet L, Jougla E, Launoy G, Grosclaude P, Buémi A, et al. Incidence of gastrointestinal cancers in France. Gastroenterol Clin Biol. 2004;28:877–81.

    Article  PubMed  Google Scholar 

  2. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics. CA Cancer J Clin. 1999;49:8–31.

    Article  PubMed  CAS  Google Scholar 

  3. Grady WM. Genetic testing for high-risk colon cancer patient. Gastroenterology. 2003;124:1574–94.

    Article  PubMed  CAS  Google Scholar 

  4. Benamouzig R, Chaussade S, Olschwang S. Polyposis coli: a practical approach. Gastroenterol Clin Biol. 2005;29:1035–9.

    Article  PubMed  Google Scholar 

  5. Penna CP, Tiret E, Kartheuser AH, Olschwang S, Parc R. Value of screening of familial adenomatous polyposis for prevention of colorectal cancer. Gastroenterol Clin Biol. 1992;16:210–4.

    PubMed  CAS  Google Scholar 

  6. Lynch HT, Smyrk T, McGinn T, Lanspa S, Cavalieri J, Lynch J, et al. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer. 1995;76:2427–33.

    Article  PubMed  CAS  Google Scholar 

  7. Nieuwenhuis MH, Vasen HFA. Correlations between mutation site in APC and phenotype of familial adenomatous polyposes (FAP): A review of the literature. Crit Rev Oncol/Hematol. 2007;61:153–61.

    Article  CAS  Google Scholar 

  8. Scott RJ, Meldrum C, Crooks R, Spigelman AD, Kirk J, Tucker K, et al. Familial adenomatous polyposis: more evidence for disease diversity and genetic heterogeneity. Gut. 2001;48:508–14.

    Article  PubMed  CAS  Google Scholar 

  9. Knudsen AL, Bisgaard ML, Bulow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003;2:43–55.

    Article  PubMed  Google Scholar 

  10. Beroud C, Soussi T. APC gene: database of germline and somatic mutation in human tumors and cell lines. Nucl Acids Res. 1996;24:121–4.

    Article  PubMed  CAS  Google Scholar 

  11. Spirio L, Olschwang S, Groden J, Robertson M, Samowitz W, Joslyn G, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993;75:951–7.

    Article  PubMed  CAS  Google Scholar 

  12. Gebert JF, Dupon C, Kadmon M, Hahn M, Herfarth C, von Knebel Doeberitz M, et al. Combined molecular and clinical approaches for the identification of families with familial adenomatous polyposis coli. Ann Surg. 1999;229:350–61.

    Article  PubMed  CAS  Google Scholar 

  13. Van der Luitj RB, Vassen HF, Tops CM, Breukel C, Fodde R, Meera Khan P. APC mutation in the alternatively spliced region of exon 9 associated with late onset of adenomatous polyposis. Hum Genet. 1995;96:705–10.

    Article  Google Scholar 

  14. Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology. 2004;127:444–51.

    Article  PubMed  Google Scholar 

  15. Lipton L, Tomlinson I. The genetics of FAP and FAP-like syndromes. Fam Cancer. 2006;5:221–6.

    Article  PubMed  CAS  Google Scholar 

  16. Moisio AL, Järvinen H, Peltomäki P. Genetic and clinical characterisation of familial adenomatous polyposis: a population based study. Gut. 2002;50:845–50.

    Article  PubMed  CAS  Google Scholar 

  17. Vasen HF, van der Luijt RB, Slors JF, Buskens E, de Ruiter P, Baeten CG, et al. Molecular genetic tests as a guide to surgical management of familial adenomatous polyposes. Lancet. 1996;348:433–5.

    Article  PubMed  CAS  Google Scholar 

  18. Wu JS, Paul P, McGannon EA, Church JM. APC genotype, polyp number, and surgical options in familial adenomatous polyposis. Ann Surg. 1998;227:57–62.

    Article  PubMed  CAS  Google Scholar 

  19. Bülow C, Vasen H, Järvinen H, Björk J, Bisgaard ML, Bülow S. Ileorectal anastomosis is appropriate for a subset of patients with familial adenomatous polyposes. Gastroenterology. 2000;119:1454–60.

    Article  PubMed  Google Scholar 

  20. Friedl W, Caspari R, Sengteller M, Uhlhaas S, Lamberti C, Jungck M, et al. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposes? Experience from 680 FAP families. Gut. 2001;48:515–21.

    Article  PubMed  CAS  Google Scholar 

  21. Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, et al. Inherited variants of MYH associated with somatic G:C → T:A mutations in colorectal tumors. Nat Genet. 2002;30:227–32.

    Article  PubMed  CAS  Google Scholar 

  22. Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, et al. Multiple colorectal adenomas, classic adenomatous polyposis and germ-line mutations in MYH. N Engl J Med. 2003;348:791–9.

    Article  PubMed  Google Scholar 

  23. Lefevre JH, Rodrigue CM, Mourra N, Bennis M, Flejou JF, Parc R, et al. Implication of MYH in colorectal polyposis. Ann Surg. 2006;244:874–80.

    Article  PubMed  Google Scholar 

  24. Bussey HJR. Familial Polyposis Coli. Baltimore: John Hopkins Univeristy Press 1975.

    Google Scholar 

  25. Johns LE, Houslton RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol. 2001;96:2292–3003.

    Article  Google Scholar 

  26. Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T, et al. Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet. 1995;4:337–40.

    Article  PubMed  CAS  Google Scholar 

  27. Houlston R, Crabtree M, Phillips R, Crabtree M, Tomlinson I. Explaining differences in the severity of familial adenomatous polyposis and the search for modifier genes. Gut. 2001;48:1–5.

    Article  PubMed  CAS  Google Scholar 

  28. Matsuo S, Eguchi S, Azuma T, Hidaka M, Yamaguchi S, Hayashi T, et al. Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case. Surg Today. 2001;31:1020–3.

    Article  PubMed  CAS  Google Scholar 

  29. Giardiello FM, Krush AJ, Petersen GM, Booker SV, Kerr M, Tong LL, et al. Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation. Gastroenterology. 1994;106:1542–7.

    PubMed  CAS  Google Scholar 

  30. Sieber OM, Segditsas S, Knudsen AL, Zhang J, Luz J, Rowan AJ, et al. Disease severity and genetic pathways in attenuated familial polyposis vary greatly but depend on the site of the germline mutation. Gut. 2006;55:1440–8.

    Article  PubMed  CAS  Google Scholar 

  31. Lamlum H, Al Tassan N, Jaeger E, Frayling I, Sieber O, Reza FB, et al. Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. Hum Mol Genet. 2000;9:2215–21.

    PubMed  CAS  Google Scholar 

  32. Sieber OM, Lamlum H, Crabtree MD, Rowan AJ, Barclay E, Lipton L, et al. Whole gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or multiple colorectal adenomas. Proc Natl Acad Sci USA. 2000;99:2954–8.

    Article  CAS  Google Scholar 

  33. Nilbert M, Fernebro J, Kristofferson U. Novel germline APC mutations in Swedish patients with familial adenomatous polyposis and Gardner syndrome. Scand J Gastroenterol. 2000;35:1200–3.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

There are no potential conflicts of interests.

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Authors and Affiliations

  1. Department of Digestive Surgery, Hopital Saint-Antoine (AP-HP), University Paris VII Pierre & Marie Curie, Paris, 75012, France

    Jérémie H. Lefevre MD, Yann Parc MD, PhD, Solen Kernéis MD, Conor Shields MD, Rolland Parc MD, FACS & Emmanuel Tiret MD

  2. Department of Pathology, Hopital Saint-Antoine (AP-HP), University Paris VII Pierre & Marie Curie, Paris, 75012, France

    Magali Svrcek MD & Jean-François Flejou MD

  3. Laboratory of Angiogenetics and Oncogenetics, Hopital Pitié-Salpétrière (AP-HP), University Paris VII Pierre & Marie Curie, Paris, 75013, France

    Chrystelle Colas MD

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  1. Jérémie H. Lefevre MD
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  2. Yann Parc MD, PhD
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  3. Magali Svrcek MD
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  4. Solen Kernéis MD
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  5. Chrystelle Colas MD
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  7. Jean-François Flejou MD
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  8. Rolland Parc MD, FACS
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  9. Emmanuel Tiret MD
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Correspondence to Jérémie H. Lefevre MD.

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Lefevre, J.H., Parc, Y., Svrcek, M. et al. APC, MYH, and the Correlation Genotype-Phenotype in Colorectal Polyposis. Ann Surg Oncol 16, 871–877 (2009). https://doi.org/10.1245/s10434-008-0297-0

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  • DOI: https://doi.org/10.1245/s10434-008-0297-0

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