title: CHEK2 I157T associates with familial and sporadic colorectal cancer.
abstract: 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.
authors.forename: O
authors.initials: O
authors.lastname: Kilpivaara
authors.forename: P
authors.initials: P
authors.lastname: Alhopuro
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
mesh_terms: D016022:Case-Control Studies; D064447:Checkpoint Kinase 2; D015179:Colorectal Neoplasms / Q000235:genetics*; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018570:Risk Assessment
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases