Familial Cancer

, 8:519 | Cite as

Cancer risk in a cohort of subjects carrying a single mismatch repair gene mutation

  • D. A. StupartEmail author
  • P. A. Goldberg
  • U. Algar
  • R. Ramesar


Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant condition, caused by germline mutations in the mismatch repair genes, that presents with colorectal cancers at a young age, as well as extracolonic tumours. One of the causative mutations is the C1528T (Exon 13) mutation of the MLH1 gene. The purpose of this study is to document the cancer risk for subjects who carry this mutation. This is a prospective cohort study of 200 subjects who carry this mutation. We calculated the risk of developing colorectal cancer only in those subjects who had not undergone surveillance colonoscopy. The incidence of extracolonic cancers (for which surveillance is not routinely offered) was determined for the entire cohort. The results of the study are among the 71 subjects who did not undergo surveillance colonoscopy, colorectal cancers occurred in 36 (51%). They occurred at a median age of 44 years (range 17–73). Using Kaplan–Meier estimates, the risk of developing a colorectal cancer by age 65 was 92%. Eighteen subjects in the cohort of 200 were diagnosed with extracolonic tumours. The most common extracolonic malignancies were breast (6/98 women) and endometrial (3/98 women). Thus this mutation has a high penetrance for colorectal cancer, but is not associated with a high risk of developing extracolonic malignancies.


Hereditary nonpolyposis colorectal cancer Screening MLH1 Mismatch repair gene Colorectal cancer 


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • D. A. Stupart
    • 1
    • 2
    Email author
  • P. A. Goldberg
    • 1
    • 2
  • U. Algar
    • 1
    • 2
  • R. Ramesar
    • 3
    • 4
  1. 1.Colorectal Unit, Department of SurgeryUniversity of Cape TownCape TownSouth Africa
  2. 2.E22 Colorectal UnitGroote Schuur HospitalObservatory, Cape TownSouth Africa
  3. 3.MRC/UCT Human Genetics Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular MedicineUniversity of Cape TownCape TownSouth Africa
  4. 4.Faculty of Health SciencesUniversity of Cape TownObservatory, Cape TownSouth Africa

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