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

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Abstract

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.

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Abbreviations

APC:

adenomatous polyposis coli

CHRPE:

congenital hypertrophy of the retinal pigment epithelium

FAP:

familial adenomatous polyposis

MYH:

Mut Y homologue

PTT:

protein truncation test

RT-PCR:

reverse transcriptase polymerase chain reaction

SSCP:

single strand conformation analysis

UCSF:

University California San Francisco

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Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology and the Comprehensive Cancer Center, University of California, San Francisco, 94115-1623, 2330 Post Street, CA, USA

    Brindusa Truta, Brian A. Allen, Peggy G. Conrad, Vivian Weinberg & Jonathan P. Terdiman

  2. Pharmacogenetics Laboratory, Clinical Molecular Immunology Research Genzyme Corporation, Framingham, Massachusetts, USA

    Glenn A. Miller & Rob Pomponio

  3. Molecular and Population Genetics Laboratory, London Research Institute, UK

    Lara R. Lipton, Germano Guerra & Ian P. M. Tomlinson

  4. Department of Veteran Affairs Medical Center, San Francisco, California, USA

    Marvin H. Sleisenger & Young S. Kim

Authors
  1. Brindusa Truta
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  2. Brian A. Allen
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  3. Peggy G. Conrad
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  4. Vivian Weinberg
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  5. Glenn A. Miller
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  6. Rob Pomponio
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  7. Lara R. Lipton
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  8. Germano Guerra
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  9. Ian P. M. Tomlinson
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  11. Young S. Kim
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  12. Jonathan P. Terdiman
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Correspondence to Jonathan P. Terdiman.

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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). https://doi.org/10.1007/s10689-004-5814-0

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  • DOI: https://doi.org/10.1007/s10689-004-5814-0

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