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Submitted on 4 Apr 2013
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Genetic variants involved in specialized DNA replication
and their relation with breast cancer risk, disease
progression and patient prognosis
Ana Brandalize, Roberto Minozzo, Lavínia Schüller-Faccini, Jean-Sebastien
Hoffman, Christophe Cazaux, Patricia Ashton-Prolla
To cite this version:
Ana Brandalize, Roberto Minozzo, Lavínia Schüller-Faccini, Jean-Sebastien Hoffman, Christophe
Cazaux, et al.. Genetic variants involved in specialized DNA replication and their relation with breast
cancer risk, disease progression and patient prognosis. São Paulo Advanced School of Comparative
Oncology, Sep 2012, Águas de São Pedro, Brazil. pp.P7. �inserm-00807779�
P O S T E R P R E S E N T A T I O N
Open Access
Genetic variants involved in specialized DNA
replication and their relation with breast cancer
risk, disease progression and patient prognosis
Ana PC Brandalize
1,2,3*, Roberto Minozzo
1, Lavínia Schüller-Faccini
1,3, Jean-Sebastien Hoffman
4, Christophe Cazaux
4,
Patricia Ashton-Prolla
1,2,3From
São Paulo Advanced School of Comparative Oncology
Águas de São Pedro, Brazil. 30 September - 6 October 2012
Background
The molecular mechanisms involved in genetic instability, which is a driving force of cancer cells from earlier stages of pathologenesis, are not fully understood. Current evi-dence shows that overexpression of Pol θ, a “DNA repair” polymerase specialized in the replication of damaged DNA, which is altered in breast tumors, is not a passive agent in tumor development and is able to predict patient outcome. Aberrant POLQ expression may be related to genetic instability, and also resistance to “replicative stress”, leading to changes in replicating parameters and consequent tumor development. The objective of this pro-ject is to analyze genetic variants related to POLQ as new population biomarkers of risk, progression and prognosis in hereditary (HBC) and sporadic (SBC) breast cancer in Brazil.
Materials and methods
Single Nucleotide Polymorphisms (SNPs) were systemati-cally identified through the NCBI database. SNPs identi-fied result in amino acid exchange in the protein and are located within exons or promoter regions. Most SNPs have not been tested in population-based studies. We recruited 211 breast cancer patients (94 SBC and 114 HBC) and 206 women without cancer. In this case-control study, we first genotyped seven SNPs (rs61757736, rs557 48151, rs41545723, rs1381057, rs587553, rs13065220, rs3806614) using Taqman Real Time PCR. Data were ana-lyzed using SPSS 18.0.
Results
Interestingly, the rs581553SNP located in a promoter region was associated with HBC (g.121265913T>C; HBC TT=16, Control TT=8; OR=2.01, CI95%= 1.32-3.32; p<0.001). Although the Chi-Square analysis did not show any statisti-cal difference between groups for the other SNPs, the HBC group showed more polymorphic genotypes than SBC and Control groups regarding the rs1381057 SNP (c.7538T>C; SBC TT=7, HBC TT=13, Control TT=8).
Conclusions
These results suggest that POLQ germline variation may be related to cancer progression in this patient group. Additional SNPs are being analyzed and the correlation between genotype and relevant clinical variables for breast cancer prognosis will be evaluated.
Financial support
CNPq, FIPE-HCPA, INAGEMP.
Author details
1Department of Genetics, Federal University of Rio Grande do Sul, Porto
Alegre, Brazil.2Experimental Research Center, Hospital de Clínicas de Porto
Alegre, Porto Alegre, Brazil.3National Institute of Populational Genetics,
INAGEMP, Porto Alegre, Brazil.4Cancer Research Center of Toulouse, INSERM
U1037, University Paul Sabatier, University of Toulouse, Toulouse Oncopole, Toulouse, France.
Published: 4 April 2013
doi:10.1186/1753-6561-7-S2-P7
Cite this article as:Brandalize et al.: Genetic variants involved in specialized DNA replication and their relation with breast cancer risk, disease progression and patient prognosis. BMC Proceedings2013 7(Suppl 2):P7.
* Correspondence: anapaulabrandalize@yahoo.com.br
1Department of Genetics, Federal University of Rio Grande do Sul, Porto
Alegre, Brazil
Full list of author information is available at the end of the article Brandalize et al. BMC Proceedings 2013, 7(Suppl 2):P7 http://www.biomedcentral.com/1753-6561/7/S2/P7
© 2013 Brandalize et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
