title: Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.
abstract: The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted.
authors.affiliation: Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Iniesta
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gorin
authors.forename: Ling-Chen
authors.initials: LC
authors.lastname: Chien
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Thomas
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Milliron
authors.forename: Julie A
authors.initials: JA
authors.lastname: Douglas
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Merajver
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005190:Family; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America / Q000208:ethnology; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases