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Low penetrance alleles as risk modifiers in familial and sporadic breast cancer

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Abstract

The aim of the study is to investigate the relevance of rs1056663 and rs2708861 HUS1 polymorphisms, and rs104548, rs2981582 and rs2910164 polymorphisms of CASP8, FGFR2 and micro RNA 146A genes, respectively, as risk modifiers in hereditary breast or ovarian cancer (BC/OC) and risk factors in sporadic BC. We performed a case–control study in 189 healthy controls (CG) and 538 BC/OC cases, 340 with familial history of BC/OC (130 carriers of BRCA1/2 mutations and 210 non-carriers) and 198 sporadic BC/OC. The polymorphisms were assessed by real-time PCR using primers and fluorescent-labelled hybridization probes. We found statistically significant differences between familial BC/OC and CG for rs1056663 and rs2708861 HSU1 polymorphisms and rs2981582 FGFR2 polymorphism, particularly in non-carriers of BRCA1/2 mutations. In this group we found statistical differences for rs1056663 HSU1 and rs2981582 FGFR2 polymorphisms (p-trend < 0.006). The logistic regression confirmed that rs2981582 FGFR2 polymorphism (OR = 2.09; 95 % CI 1.35, 3.20) and the interaction between rs1056663 and rs2708861 HUS1 polymorphisms increased the risk of cancer (OR = 1.87; 95 % CI 1.19, 2.92). Furthermore, we found that the presence of rs1056663 and rs2708861 HUS1 polymorphisms is associated with early age of presentation of BC (p = 0.015) in the group of non-carriers of BRCA1/2 mutations. In addition, no association of the polymorphisms studied in sporadic BC was observed. In conclusion, the HUS1 and FGFR2 polymorphisms act as risk BC modifiers in familial BC/OC, particularly in the group of non-carriers of BRCA1/2 mutations.

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Acknowledgments

We should express here our gratitude for the good work and dedication of Alma María Olegario Serra, Degree in Biology, Gema Pérez Simó and Lidia González Martínez, laboratory technician, contracted by the project. This study has been funded by the grants from the “Fundación Gent per Gent” (Ref 40/09) and from the “Consellería de Sanitad de la Generalitat Valenciana para el Desarrollo de Proyectos de Investigación en Matería Sanitaria” (AP-181/10).

Conflict of interest

None declared.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Service of Clinical Analysis, Escuela de Enfermería 7ª, Hospital La Fe, Hospital Universitario La Fe; Avd. Campanar 21, 46009, Valencia, Spain

    Eva Esteban Cardeñosa, Inmaculada de Juan Jiménez, Sarai Palanca Suela, Eva Barragán González, Oscar Fuster Lluch & Pascual Bolufer Gilabert

  2. Genetic Counseling Unit, Hospital Clínico, Valencia, Spain

    Isabel Chirivella González

  3. Genetic Counseling Unit, Hospital La Fe, Valencia, Spain

    Ángel Segura Huerta

  4. Service of Clinical Oncology, Hospital La Fe, Valencia, Spain

    Ana Santaballa Beltran

  5. Breast Cancer Prevention Unit, Radiodiagnosis, Escuela de Enfermería, Hospital La Fe, Valencia, Spain

    María Casals El Busto

  6. Department of Statistics and Operations Research, Faculty of Mathematics, University of Valencia, Valencia, Spain

    José Bermúdez Edo

Authors
  1. Eva Esteban Cardeñosa
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  2. Inmaculada de Juan Jiménez
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  3. Sarai Palanca Suela
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  4. Isabel Chirivella González
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  5. Ángel Segura Huerta
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  6. Ana Santaballa Beltran
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  7. María Casals El Busto
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  8. Eva Barragán González
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  9. Oscar Fuster Lluch
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  10. José Bermúdez Edo
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  11. Pascual Bolufer Gilabert
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Corresponding author

Correspondence to Pascual Bolufer Gilabert.

Additional information

This study is conducted on behalf of the Group for Assessment for Hereditary Cancer of Valencian Community.

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Esteban Cardeñosa, E., de Juan Jiménez, I., Palanca Suela, S. et al. Low penetrance alleles as risk modifiers in familial and sporadic breast cancer. Familial Cancer 11, 629–636 (2012). https://doi.org/10.1007/s10689-012-9563-1

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  • DOI: https://doi.org/10.1007/s10689-012-9563-1

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