%0 Journal Article
%T TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study
%A Magda A Blaut
%A Natalia V Bogdanova
%A Michael Bremer
%A Johann H Karstens
%A Peter Hillemanns
%A Thilo D£¿rk
%J Journal of Negative Results in BioMedicine
%D 2010
%I BioMed Central
%R 10.1186/1477-5751-9-9
%X Only a small proportion of breast cancer cases can be attributed to mutations in high-penetrance genes such as BRCA1 or BRCA2, and much of the remaining cases are attributed to more common gene variants with lower penetrance [1,2]. As many of the hitherto known susceptibility factors have been implicated in the cellular responses to DNA double-strand breaks and replication stress, there is considerable interest in genetic variants of additional proteins involved in these pathways [2].TOPBP1 encodes a protein that shares homology to BRCA1, is aberrantly expressed in breast carcinomas and has a critical role in DNA damage and replication checkpoint pathways [3-7]. TOPBP1 encodes a 1522 amino acid BRCT domain protein that interacts with DNA topoisomerase II¦Â and is involved in ATM/ATR-mediated DNA damage and replication checkpoint pathways [3-6]. Reduced or aberrantly localized TopBP1 expression has been observed in a significant proportion of breast cancer specimens [7]. Functional TOPBP1 variants therefore represent plausible candidate breast cancer susceptibility alleles. A recent sequencing and case-control association study has assessed the role of germ-line variants in Finnish breast and ovarian cancer patients [8]. The novel Arg309Cys substitution was observed at significantly higher frequency in 125 familial breast and/or ovarian cancer patients compared to 697 healthy controls (15.2% versus 7.0%; P = 0.002), and a 2.4-fold increase in risk was suggested [8]. We aimed to corroborate this finding in a hospital-based series of 1064 German breast cancer patients and 1014 population controls.Our German study population consisted of a hospital-based series of 1012 unselected breast cancer patients who were treated at the Department of Radiation Oncology at Hannover Medical School from 1996-1999 and an additional small series of 52 patients with bilateral breast cancer collected later from the same hospital. Median age at onset of breast cancer was 57 years in this p
%U http://www.jnrbm.com/content/9/1/9