Article Text

Download PDFPDF
CHEK2 I157T associates with familial and sporadic colorectal cancer
  1. O Kilpivaara1,
  2. P Alhopuro2,*,
  3. P Vahteristo2,*,
  4. L A Aaltonen2,
  5. H Nevanlinna1
  1. 1Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
  2. 2Department of Medical Genetics, University of Helsinki, Helsinki, Finland
  1. Correspondence to:
 Heli Nevanlinna
 Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Biomedicum Helsinki, PO Box 700, FIN-00029 HUS, Finland; heli.nevanlinna{at}


Background: Recently, a functionally defective CHEK2 variant I157T has been proposed to associate with an increased risk of several types of cancer. We investigated the CHEK2 I157T variant for colorectal cancer (CRC) predisposition in a large population based study including a significant number of familial CRC cases.

Methods: We screened the CHEK2 I157T variant in a population based series of 1042 Finnish CRC patients using restriction fragment length polymorphism. Mutation status was studied for correlation with clinical characteristics and family history of CRC and other cancers.

Results: The frequency of CHEK2 I157T was significantly higher in CRC patients (7.8%, 76/972) than in healthy population controls (5.3%, 100/1885) (OR = 1.5, 95% CI 1.1 to 2.1, p = 0.008). The significant association of CHEK2 I157T with CRC was observed among patients with (10.4%, 14/135) and without (7.4%, 62/837) a family history of CRC (OR = 2.1, 95% CI 1.1 to 3.7, p = 0.01; OR = 1.4, 95% CI 1.0 to 2.0, p = 0.03; respectively). A trend towards higher variant frequency was also noted among patients with multiple primary tumours and a family history of any cancer.

Conclusions:CHEK2 I157T associates with an increased risk of CRC: the association was observed both among familial and sporadic CRC patients. Furthermore, the higher frequency of I157T among patients with multiple primary tumours as well as those with a family history of any cancer supports a role for CHEK2 I157T as a susceptibility allele for multiple cancer types.

  • CHEK2, cell cycle checkpoint kinase 2
  • CRC, colorectal cancer
  • FHA, forkhead associated
  • MMR, mismatch repair
  • RER, replication error
  • RFLP, restriction fragment length polymorphism
  • SCD, SQ/TQ cluster domain
  • CHEK2
  • colorectal cancer
  • susceptibility

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • * These authors contributed equally to this article

  • This study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland, Finnish Cancer Society, Sigrid Juselius Foundation, Foundation of the Finnish Cancer Institute, Finnish Cultural Foundation Uusimaa, Ida Montin Foundation, and Emil Aaltonen Foundation

  • Competing interests: none declared