Skip to main content
Log in

A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history

  • Published:
Familial Cancer Aims and scope Submit manuscript


Objectives: Adenomatous polyposis of the colon is often secondary to an inherited mutation in adenomatous polyposis coli (APC) gene, however, approximately one third of patients have no family history of the disease. We studied the phenotype and genotype of adenomatous polyposis in patients without a family history. Methods: A cohort of 57 unrelated adenomatous polyposis patients were evaluated. Seventeen patients with no family history were compared with 40 patients who had a positive family history of the disease. Family history and medical records were collected and analyzed. Germline APC and Mut Y homologue (MYH) testing was undertaken. Results: Patients without a family history were diagnosed with polyposis at an older age (41 years vs. 32 years) and presenting more frequently with symptoms (76 vs 20, P < 0.05). The number of colonic polyps and frequency of extracolonic manifestation associated with adenomatous polyposis did not differ between the two groups. APC mutations were detected less frequently among patients without a family history of the disease (4 out of 17 vs 25 out of 40, P=0.007), even among those with greater than 100 colorectal adenomas (4 out of 12 versus 21 out of 29, P=0.03). One homozygous MYH mutation carrier (G382D) was detected among the six patients without a family history and without a germline APC mutation who were tested. Conclusions: Adenomatous polyposis patients without a family history are usually diagnosed with symptoms, and at a later age. Phenotypically, they are similar to those with a family history. However, germline APC mutations are detected far less frequently in patients without a family history. A small percentage of these cases may be secondary to biallelic germline MYH mutations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others



adenomatous polyposis coli


congenital hypertrophy of the retinal pigment epithelium


familial adenomatous polyposis


Mut Y homologue


protein truncation test


reverse transcriptase polymerase chain reaction


single strand conformation analysis


University California San Francisco


  1. LA Knudsen ML Bisgaard S. Bulow (2003) ArticleTitleAttenuated familial adenomatous polyposis (AFAP) A review of the literature. Fam Cancer 2 43–55

    Google Scholar 

  2. C Soravia T Berk L Madlensky et al. (1998) ArticleTitleGenotype-phenotype correlations in attenuated adenomatous polyposis coli Am J Hum Genet 62 1290–301 Occurrence Handle10.1086/301883 Occurrence Handle1:CAS:528:DyaK1cXlslCiur8%3D Occurrence Handle9585611

    Article  CAS  PubMed  Google Scholar 

  3. AM Watson B Zehnbauer I Kodner et al. (1995) ArticleTitleGenetic diagnosis of familial adenomatous polyposis Lab Med Newslett 3 1–6

    Google Scholar 

  4. SN Fearnhead LJ Wilding FW. Bodmer (2002) ArticleTitleGenetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis Br Med Bull 64 27–43 Occurrence Handle10.1093/bmb/64.1.27 Occurrence Handle1:CAS:528:DC%2BD38XosFOgsrg%3D Occurrence Handle12421723

    Article  CAS  PubMed  Google Scholar 

  5. ML Bisgaard K Fenger S Bullow et al. (1994) ArticleTitleFamilial adenomatous polyposis (FAP): frequency, penetrance and mutation rate Hum Mutat 3 121–5 Occurrence Handle1:STN:280:ByuB2Mfhs1Q%3D Occurrence Handle8199592

    CAS  PubMed  Google Scholar 

  6. S. Bulow (2003) ArticleTitleResult of national registration of familial adenomatous polyposis Gut 52 742–6 Occurrence Handle1:STN:280:DC%2BD3s7ntlKjtg%3D%3D Occurrence Handle12692062

    CAS  PubMed  Google Scholar 

  7. L Bertario A Russo P Sala et al. (2003) ArticleTitleMultiple approach to the exploration of genotype–phenotype correlations in familial adenomatous polyposis J Clin Oncol 21 1698–707 Occurrence Handle10.1200/JCO.2003.09.118 Occurrence Handle1:CAS:528:DC%2BD2cXpsVWqsbs%3D Occurrence Handle12721244

    Article  CAS  PubMed  Google Scholar 

  8. C Beroud T. Soussi (1996) ArticleTitleAPC gene: database of germline and somatic mutations in human tumors and cell lines Nucleic Acid Res 24 121–4 Occurrence Handle10.1093/nar/24.1.121 Occurrence Handle1:CAS:528:DyaK28XnsV2qsg%3D%3D Occurrence Handle8594558

    Article  CAS  PubMed  Google Scholar 

  9. G Lal S. Gallinger (2000) ArticleTitleFamilial adenomatous polyposis Sem Surg Oncol 18 314–23 Occurrence Handle10.1002/(SICI)1098-2388(200006)18:4<314::AID-SSU6>3.0.CO;2-9 Occurrence Handle1:STN:280:DC%2BD3c3ms1CktA%3D%3D

    Article  CAS  Google Scholar 

  10. JH. Jarvinen (2003) ArticleTitleGenetic testing for polyposis: practical and ethical aspects Gut 52 19–22 Occurrence Handle10.1136/gut.52.suppl_2.ii19

    Article  Google Scholar 

  11. KMB Heininiman W Weber M Attenhofer et al. (1998) ArticleTitlePhenotypic differences in familial adenomatous polyposis based on APC gene mutation status Gut 43 675–79 Occurrence Handle1:STN:280:DyaK1M%2FntFamtA%3D%3D Occurrence Handle9824350

    CAS  PubMed  Google Scholar 

  12. MO Sieber L Lipton M Crabtree et al. (2003) ArticleTitleMultiple colorectal adenomas, classic adenomatous polyposis and germ-line mutations in MYH N Engl J Med 343 791–9 Occurrence Handle10.1056/NEJMoa025283

    Article  Google Scholar 

  13. R Vande Luijt PM Knan H Vasen et al. (1994) ArticleTitleRapid detection of translation-terminating mutations at the adenomatous poliposis coli (APC) gene by direct protein truncation test Genomics 20 1–4 Occurrence Handle10.1006/geno.1994.1119 Occurrence Handle8020934

    Article  PubMed  Google Scholar 

  14. M Orita Y Suzuky T Sekiya et al. (1989) ArticleTitleRapid and sensitive detection of point mutation and DNA polymorphism using the polimerase chain reaction Genomics 5 874–9 Occurrence Handle1:CAS:528:DyaK3cXjtFKksQ%3D%3D Occurrence Handle2687159

    CAS  PubMed  Google Scholar 

  15. M Ponzde Leon P Benatti A Percesepe et al. (1999) ArticleTitleClinical features and genotype–phenotype correlations in 41 Italian families with adenomatosis coli Ital J Gastroenterol Hepatol 31 850–60 Occurrence Handle1:STN:280:DC%2BD3c7jsVyruw%3D%3D Occurrence Handle10669993

    CAS  PubMed  Google Scholar 

  16. K Heininiman A Thompson A Locher et al. (2001) ArticleTitleNontruncating APC germl-line mutations and mismach repair deficiency play a minor role in APC mutation-negative polyposis Cancer Res 61 7616–22 Occurrence Handle11606402

    PubMed  Google Scholar 

  17. A-L Moisio H Jarvinen P. Peltomaki (2002) ArticleTitleGenetic and clinical characterisation of familial adenomatous polyposis: a population based study Gut 50 845–50 Occurrence Handle10.1136/gut.50.6.845 Occurrence Handle1:CAS:528:DC%2BD38XkvVGkt7c%3D Occurrence Handle12010888

    Article  CAS  PubMed  Google Scholar 

  18. RB Rustin GD Jagelman E McGannon et al. (1990) ArticleTitleSpontaneous mutation in familial adenomatous polyposis Dis Colon Rectum 33 52–5 Occurrence Handle1:STN:280:By%2BC3cjmtlY%3D Occurrence Handle2153067

    CAS  PubMed  Google Scholar 

  19. M Giarola L Stagi S Presciuttini et al. (1999) ArticleTitleScreening for mutations of the APC gene in 66 Italian familial adenomatous polyposis patients: evidence for phenotypic differences in cases with and without identified mutations Hum Mutat 13 116–23 Occurrence Handle10.1002/(SICI)1098-1004(1999)13:2<116::AID-HUMU3>3.0.CO;2-2 Occurrence Handle1:CAS:528:DyaK1MXhtFKit7k%3D Occurrence Handle10094547

    Article  CAS  PubMed  Google Scholar 

  20. W Friedl R Caspari M Sengteller et al. (2001) ArticleTitleCan APC mutation analysis contribute to the therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families Gut 48 515–21 Occurrence Handle10.1136/gut.48.4.515 Occurrence Handle1:CAS:528:DC%2BD3MXislyhurg%3D Occurrence Handle11247896

    Article  CAS  PubMed  Google Scholar 

  21. N Gavert Y Yaron T Naiman et al. (2002) ArticleTitleMolecular analysis of the APC gene in 71 Israeli families: 17 novel mutations Hum Mutat 19 664–70 Occurrence Handle10.1002/humu.9037 Occurrence Handle12007223

    Article  PubMed  Google Scholar 

  22. F Giardello JD Brensinger G. Peterson (2001) ArticleTitleAGA technical review on hereditary colorectal cancer and genetic testing Gastroenterology 121 198–213 Occurrence Handle1:CAS:528:DC%2BD3MXlt1yktLs%3D Occurrence Handle11438509

    CAS  PubMed  Google Scholar 

  23. SJ Laken N Papadopoulos et al. (1999) ArticleTitleAnalysis of masked mutations in familial adenomatous polyposis Proc Natl Acad Sci USA 96 2322–6 Occurrence Handle10.1073/pnas.96.5.2322 Occurrence Handle1:CAS:528:DyaK1MXhvVSqt7c%3D Occurrence Handle10051640

    Article  CAS  PubMed  Google Scholar 

  24. AD LamlunH Tassan E Jaeger et al. (2000) ArticleTitleGermline APC variants in patients with multiple adenomas, with evidence for the particular importance of E1317Q Hum Mol Genet 9 2215–21 Occurrence Handle1:CAS:528:DC%2BD3cXnt1yntL4%3D Occurrence Handle11001924

    CAS  PubMed  Google Scholar 

  25. RJ Sampson S DolwaniS Jones et al. (2003) ArticleTitleAutosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH Lancet 362 39–41 Occurrence Handle1:CAS:528:DC%2BD3sXltF2isrY%3D Occurrence Handle12853198

    CAS  PubMed  Google Scholar 

  26. L Wang ML Baudhuin AL. Boardman et al. (2004) ArticleTitleMYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps Gastroenterology 127 9–16 Occurrence Handle10.1053/j.gastro.2004.03.070 Occurrence Handle1:CAS:528:DC%2BD2cXmsVShsr4%3D Occurrence Handle15236166

    Article  CAS  PubMed  Google Scholar 

  27. T Venesio S Molatore F Cattaneo et al. (2004) ArticleTitleHigh frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis Gastroenterology 126 1681–5 Occurrence Handle1:CAS:528:DC%2BD2cXlsFaqsrk%3D Occurrence Handle15188161

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Jonathan P. Terdiman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Truta, B., Allen, B.A., Conrad, P.G. et al. A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history. Familial Cancer 4, 127–133 (2005).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: