title: Colorectal cancer and the CHEK2 1100delC mutation.
abstract: The CHEK2 1100delC mutation was recently identified as a low-penetrance breast cancer susceptibility allele. The mutation occurred more frequently in families with clustering of breast and colorectal cancers (CRCs) than in families with clustering of breast cancer only. Hence, the 1100delC mutation could also be a low-penetrance CRC susceptibility allele. To test this hypothesis, we examined the mutation in 629 unselected CRC cases, 230 controls, and 105 selected CRCs diagnosed in patients before age 50. The mutation was observed in 1.6% of unselected patients and in 0.3% of controls (Not significant (NS)). After stratifying unselected patients according to defined genetic risk (on the basis of age at diagnosis and family history of colorectal and endometrial cancer), the highest frequency was observed in high-risk patients (12.5%), followed by moderate-risk patients (3.3%), and was lowest in low-risk patients (1.0%, P(trend) 0.014). In selected patients, 1.6% carried the mutation (NS). Subgroup analyses for tumor localization, gender, and age at diagnosis did not reveal an association with the 1100delC genotype. In addition, a pooled analysis, combining data of one published study in unselected CRC cases and our study, also did not reveal an association. In conclusion, the frequency of the 1100delC genotype was neither significantly increased in unselected CRC patients nor in selected CRC patients diagnosed before age 50. However, after stratifying unselected CRC patients according to defined genetic risk, a significant trend of increasing frequency was observed. Together, the results are consistent with a low-penetrance effect (OR 1.5-2.0) of the CHEK2 1100delC on CRC risk. Large case-control studies are required to clarify the exact role of the CHEK2 1100delC mutation in CRC.
authors.affiliation: Department of Gastroenterology, University of Groningen Medical Center, The Netherlands.
authors.forename: Mirjam M
authors.initials: MM
authors.lastname: de Jong
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Te Meerman
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: Mulder
authors.forename: Gerrit
authors.initials: G
authors.lastname: van der Steege
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruinenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.forename: Renée C
authors.initials: RC
authors.lastname: Niessen
authors.forename: Maran J W
authors.initials: MJ
authors.lastname: Berends
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sijmons
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kleibeuker
mesh_terms: D064447:Checkpoint Kinase 2; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases