Synergistic interaction of variants in CHEK2 and BRCA2 on breast cancer risk.
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.
Serrano-Fernández
Pablo
P
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. ihcc@pabloserrano.eu
Debniak
Tadeusz
T
Górski
Bohdan
B
Bogdanova
Natalia
N
Dörk
Thilo
T
Cybulski
Cezary
C
Huzarski
Tomasz
T
Byrski
Tomasz
T
Gronwald
Jacek
J
Wokołorczyk
Dominika
D
Narod
Steven A
SA
Lubiński
Jan
J
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
D024682:BRCA2 Protein; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases