title: No increased susceptibility to breast cancer from combined CHEK2 1100delC genotype and the HLA class III region risk factors.
abstract: CHEK2 is low-penetrance breast cancer susceptibility gene. The 1100delC mutation may interact with variants/mutations in other breast cancer susceptibility loci. We identified a risk haplotype in the HLA class III region in breast cancer patients [de Jong MM, Nolte IM, de Vries EGE, et al. The HLA class III subregion is responsible for an increased breast cancer risk. Hum Mol Genet 2003, 12, 2311-2319] and tested whether it interacted with 1100delC mutation. The CHEK2 1100delC mutation was analysed in the same series of patients and controls as in the HLA breast cancer study. In 962 unselected breast cancer patients, the 1100delC mutation was observed in 2.9% and in 367 controls in 1.4% (NS). The highest 1100delC frequency occurred in high-risk (4.4%), followed by moderate-risk (3.8%), and lowest in low genetic risk patients (2.4%, P(trend) 0.029). In HLA risk haplotype carriers no increased breast cancer risk was observed in the presence of 1100delC mutation. Patients more often had one than both genetic risk factors. The 1100delC mutation and the HLA risk haplotype confer increased breast cancer risks, but an interactive effect on breast cancer between both factors is unlikely. In contrast, the effect of 1100delC mutation on breast cancer risk was limited to individuals without HLA risk haplotype, suggesting a mutual excluding effect between these risk factors.
authors.affiliation: Department of Medical Oncology, University Medical Centre Groningen, P.O. Box 30.001, 9700 RB Groningen, 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: Elvira
authors.initials: E
authors.lastname: Oosterom
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruinenberg
authors.forename: Gerrit van der
authors.initials: Gv
authors.lastname: Steege
authors.forename: Jan C
authors.initials: JC
authors.lastname: Oosterwijk
authors.forename: Annemarie H
authors.initials: AH
authors.lastname: van der Hout
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D006680:HLA Antigens; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases