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The BARD1 Cys557Ser variant and risk of familial breast cancer in a South-American population

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Abstract

Since the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case–control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2–10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age <50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36–18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations.

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Acknowledgments

The authors thank the many families who participated in the research studies described in this article. We acknowledge the Breast Cancer Group of CONAC: Maria Teresa Barrios, Angelica Soto, Rossana Recabarren, Leticia Garcia, Karen Olmos and Paola Carrasco; and Lorena Seccia for her technical assistance. This work was grant support from FONDECYT 1110089, and Corporación Nacional del Cáncer (CONAC).

Conflict of interest

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Authors and Affiliations

  1. Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, P. O. Box 70061, Santiago, Chile

    Patricio Gonzalez-Hormazabal, Rafael Blanco, Ignacio Carrera & Lilian Jara

  2. Clínica Las Condes, Santiago, Chile

    Jose M. Reyes & Octavio Peralta

  3. National Cancer Society (Corporación Nacional del Cáncer—CONAC), Santiago, Chile

    Teresa Bravo

  4. Department of Ginaecology and Obstetrics, School of Medicine, University of Chile, Av. Santa Rosa 1234, Santiago, Chile

    Octavio Peralta

  5. Clínica Santa María, Santiago, Chile

    Fernando Gomez & Enrique Waugh

  6. School of Medicine and Clínica Alemana, Universidad del Desarrollo, Santiago, Chile

    Sonia Margarit

  7. Clínica Dávila, Av. Recoleta 464, Santiago, Chile

    Gladys Ibañez

  8. Hospital San José, San José 1196, Santiago, Chile

    Gladys Ibañez

  9. Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    Jose L. Santos

Authors
  1. Patricio Gonzalez-Hormazabal
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  2. Jose M. Reyes
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  3. Rafael Blanco
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  4. Teresa Bravo
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  7. Fernando Gomez
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  8. Enrique Waugh
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  9. Sonia Margarit
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  10. Gladys Ibañez
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  11. Jose L. Santos
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  12. Lilian Jara
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Corresponding author

Correspondence to Lilian Jara.

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Gonzalez-Hormazabal, P., Reyes, J.M., Blanco, R. et al. The BARD1 Cys557Ser variant and risk of familial breast cancer in a South-American population. Mol Biol Rep 39, 8091–8098 (2012). https://doi.org/10.1007/s11033-012-1656-2

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  • DOI: https://doi.org/10.1007/s11033-012-1656-2

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