TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study.
The DNA double strand break repair gene TOPBP1 has been suggested as a breast cancer susceptibility gene and a missense variant Arg309Cys was observed at elevated frequency in familial breast cancer cases compared to healthy controls from Finland. We found the Arg309Cys allele at a 13% carrier frequency in a hospital-based series of 1064 German breast cancer patients and at a 14% carrier frequency in 1014 population controls (OR 0.89, 95%CI 0.69-1.15; p = 0.4). Arg309Cys carriers were not enriched among patients with a family history of breast cancer (OR = 0.87, 95%CI 0.53-1.43, p = 0.6) and were slightly underrepresented in patients with bilateral disease (OR = 0.49, 95%CI = 0.24-0.99; p = 0.047). In the latter group, the mean age at diagnosis was 62 years in carriers and 54 years in non-carriers (p = 0.004). We conclude that there is no evidence for the TOPBP1*Arg309Cys variant to confer an increased risk for breast cancer in the German population.
Clinics of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Magda A
MA
Blaut
Natalia V
NV
Bogdanova
Michael
M
Bremer
Johann H
JH
Karstens
Peter
P
Hillemanns
Thilo
T
Dörk
D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005858:Germany; D006761:Hospitals; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D002352:Carrier Proteins; D003062:Codon; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human