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Báo cáo khoa hoc:" TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study | Blaut et al. Journal of Negative Results in BioMedicine 2010 9 9 http www.jnrbm.eom content 9 1 9 r M 1 JOURNAL OF NEGATIVE RESULTS IN BIOMEDICINE BRIEF REPORT Open Access TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study Magda A Blaut1 Natalia V Bogdanova1 2 Michael Bremer2 Johann H Karstens2 Peter Hillemanns1 Thilo Dork1 Abstract 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. Findings 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 . .