Elsevier

The Lancet

Volume 343, Issue 8898, 12 March 1994, Pages 629-632
The Lancet

Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer

https://doi.org/10.1016/S0140-6736(94)92634-4Get rights and content

Abstract

The clinical course of familial adenomatous polyposis (FAP) varies considerably between patients. Prediction of the severity of the disease is important in the interest of effective cancer prevention. We examined whether age at diagnosis of FAP due to gastrointestinal symptoms and age at death due to colorectal cancer are related to the site of mutation in the responsible gene. 225 families with FAP were screened for mutations. The deletion of 5 base pairs at codon 1309 within exon 15 (known to be the most common mutation) was identified in 20 families; other mutations within exons 7-15 were found in 49 families. In patients with the 5 base-pair deletion at codon 1309, gastrointestinal symptoms and death from colorectal cancer occurred about 10 years earlier than in patients with other mutations. The 1309 mutation leads to development of colonic polyps at a younger age, thus giving rise to an earlier malignant tranformation. This relationship should be taken into account in strategies for preventing cancer in patients with FAP.

References (27)

  • M. Mandl et al.

    Frequency of common and novel inactivating APC mutations in 202 families with familial adenomatous polyposis

    Hum Molec Genet

    (1994)
  • L. Varesco et al.

    identification of APC gene mutations in Italian adenomatous polyposis coli patients by PCR-SSCP analysis

    Am J Hum Genet

    (1993)
  • J. Groden et al.

    Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals

    Am J Hum Genet

    (1993)
  • Cited by (214)

    • Pediatric Polyposis Syndromes

      2020, Pediatric Gastrointestinal and Liver Disease, Sixth Edition
    • Hereditary gastrointestinal carcinomas and their precursors: An algorithm for genetic testing

      2018, Seminars in Diagnostic Pathology
      Citation Excerpt :

      Remarkably, whole gene deletions also cause classical rather than severe FAP.104 Patients with mutations near the 5′ and 3′end of APC and alternatively spliced regions in exon 9 usually develop AFAP.104–112 FAP Patients with thyroid cancer show mutations throughout the APC gene, but all cause absence or truncation of the β-catenin binding site consisting of 20-amino acid repeats (20-AARs) in the germline and somatic mutated allele.113

    • Screening for Hereditary Cancer in Latin America

      2018, Genomic Medicine in Emerging Economies: Genomics for Every Nation
    • Genetics

      2018, Principles and Applications of Molecular Diagnostics
    • Screening for hereditary cancer in Latin America

      2018, Genomic Medicine in Emerging Economies: Genomics for Every Nation
    • Hereditary Colorectal Cancer Syndromes

      2017, Surgical Clinics of North America
    View all citing articles on Scopus
    View full text