Molecular Biology Reports

, Volume 41, Issue 6, pp 3715–3722 | Cite as

Association of genetic variants at TOX3, 2q35 and 8q24 with the risk of familial and early-onset breast cancer in a South-American population

  • Isabel Elematore
  • Patricio Gonzalez-Hormazabal
  • Jose M. Reyes
  • Rafael Blanco
  • Teresa Bravo
  • Octavio Peralta
  • Fernando Gomez
  • Enrique Waugh
  • Sonia Margarit
  • Gladys Ibañez
  • Carmen Romero
  • Janara Pakomio
  • Gigia Roizen
  • Gabriella A. Di Capua
  • Lilian JaraEmail author


Recent Genome-Wide Association Studies have identified several single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) among women of Asian, European, and African-American ancestry. Nevertheless, the contribution of these variants in the South American population is unknown. Furthermore, there is little information about the effect of these risk alleles in women with early BC diagnosis. In the present study, we evaluated the association between rs3803662 (TOX3, also known as TNRC9), rs13387042 (2q35), and rs13281615 (8q24) with BC risk in 344 Chilean BRCA1/2-negative BC cases and in 801 controls. Two SNPs, rs3803662 and rs13387042, were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC. The risk of BC increased in a dose-dependent manner with the number of risk alleles (P-trend < 0.0001 and 0.0091, respectively). The odds ratios for BC in familial BC and in early-onset non-familial BC were 3.76 (95 %CI 1.02–13.84, P = 0.046) and 8.0 (95 %CI 2.20–29.04, P = 0.002), respectively, for the maximum versus minimum number of risk alleles. These results indicate an additive effect of the TOX3 rs3803662 and 2q35 rs13387042 alleles for BC risk. We also evaluated the interaction between rs3803662 and rs13387042 SNPs. We observed an additive interaction only in non-familial early-onset BC cases (AP = 0.72 (0.28–1.16), P = 0.001). No significant association was observed for rs13281615 (8q24) with BC risk in women from the Chilean population. The strongly increased risk associated with the combination of low-penetrance risk alleles supports the polygenic inheritance model of BC.


Breast cancer Polymorphisms TOX3 TNRC9 2q35 8q24 



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.

Conflict of interest

Corporación Nacional del Cáncer.

The authors declare that they have no competing interests.

Grant sponsor

Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT). Grant number: 1110081.


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Isabel Elematore
    • 1
  • Patricio Gonzalez-Hormazabal
    • 1
  • Jose M. Reyes
    • 2
  • Rafael Blanco
    • 1
  • Teresa Bravo
    • 3
  • Octavio Peralta
    • 2
    • 4
  • Fernando Gomez
    • 5
  • Enrique Waugh
    • 5
  • Sonia Margarit
    • 6
  • Gladys Ibañez
    • 7
    • 8
  • Carmen Romero
    • 9
  • Janara Pakomio
    • 1
  • Gigia Roizen
    • 1
  • Gabriella A. Di Capua
    • 1
  • Lilian Jara
    • 1
    Email author
  1. 1.Human Genetics Program, Institute of Biomedical Sciences (ICBM)School of Medicine, University of ChileSantiagoChile
  2. 2.Clínica Las CondesSantiagoChile
  3. 3.National Cancer Society (Corporación Nacional del Cáncer –CONAC-)SantiagoChile
  4. 4.Department of Ginaecology and ObstetricsSchool of Medicine, University of ChileSantiagoChile
  5. 5.Clínica Santa MaríaSantiagoChile
  6. 6.School of Medicine and Clínica AlemanaUniversidad del DesarrolloSantiagoChile
  7. 7.Clínica DávilaSantiagoChile
  8. 8.Hospital San JoséSantiagoChile
  9. 9.Endocrinology and Reproductive Biology LaboratoryClinical Hospital University of Chile (HCUCH)SantiagoChile

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