title: Synergistic interaction of variants in CHEK2 and BRCA2 on breast cancer risk.
abstract: We studied the effects of BRCA2 and CHEK2 variants on breast cancer risk in two case-control series from Poland and Belarus. The missense BRCA2 variant T1915M was associated with a significant reduction in breast cancer risk (OR = 0.62; 95% CI 0.49-0.79; P = 0.0007). Modest increases of breast cancer risk were observed for the four analysed CHEK2 variants (I157T, 1100delC, IVS2 + 1G > A and del5395) (OR = 2.2; 95% 1.7-2.8; P = 0.0001). The highest risk was observed among women who carried both a BRCA2 and a CHEK2 variant (OR = 5.7; 95% CI 1.7-19; P = 0.006). We observed a statistically significant interaction effect between CHEK2 mutations and the BRCA2 substitution (P = 0.03). These data suggest that the BRCA2 T1915M polymorphism alone might be associated with a reduced risk of breast cancer, but among CHEK2 mutation carriers, it may lead to an unexpectedly high risk.
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. ihcc@pabloserrano.eu
authors.forename: Pablo
authors.initials: P
authors.lastname: Serrano-Fernández
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Dominika
authors.initials: D
authors.lastname: Wokołorczyk
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D024682:BRCA2 Protein; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases