Breast Cancer Research and Treatment

, Volume 138, Issue 3, pp 861–868

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy

  • L. Ottini
  • V. Silvestri
  • C. Saieva
  • P. Rizzolo
  • I. Zanna
  • M. Falchetti
  • G. Masala
  • A. S. Navazio
  • V. Graziano
  • S. Bianchi
  • S. Manoukian
  • M. Barile
  • P. Peterlongo
  • C. D’Amico
  • L. Varesco
  • S. Tommasi
  • A. Russo
  • G. Giannini
  • L. Cortesi
  • A. Viel
  • M. Montagna
  • P. Radice
  • D. Palli
Epidemiology
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Abstract

It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common low-penetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 age-matched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43–2.05; p = 0.0001), rs3803662/TOX3 (OR = 1.59; 95 % CI: 1.32–1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05–1.50; p = 0.013). Furthermore, we showed that the prevalence of the risk genotypes of ESR1 tended to be higher in ER− tumors (p = 0.062). In a case–case multivariate analysis, a statistically significant association between ESR1 and ER− tumors was found (OR = 1.88; 95 % CI: 1.03–3.49; p = 0.039). Overall, our data, based on a large and well-characterized MBC series, support the hypothesis that common low-penetrance BC susceptibility alleles play a role in MBC susceptibility and, interestingly, indicate that ESR1 is associated with a distinct tumor subtype defined by ER-negative status.

Keywords

Male breast cancer BRCA1/2 Low-penetrance breast cancer alleles SNPs Clinicopathological characteristics ER/PR status 

Supplementary material

10549_2013_2459_MOESM1_ESM.doc (78 kb)
Supplementary material 1 (DOC 78 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • L. Ottini
    • 1
  • V. Silvestri
    • 1
  • C. Saieva
    • 2
  • P. Rizzolo
    • 1
  • I. Zanna
    • 2
  • M. Falchetti
    • 1
  • G. Masala
    • 2
  • A. S. Navazio
    • 1
  • V. Graziano
    • 1
  • S. Bianchi
    • 3
  • S. Manoukian
    • 4
  • M. Barile
    • 5
  • P. Peterlongo
    • 6
  • C. D’Amico
    • 7
  • L. Varesco
    • 8
  • S. Tommasi
    • 9
  • A. Russo
    • 10
  • G. Giannini
    • 1
  • L. Cortesi
    • 11
  • A. Viel
    • 12
  • M. Montagna
    • 13
  • P. Radice
    • 6
  • D. Palli
    • 2
  1. 1.Department of Molecular Medicine“Sapienza” University of RomeRomeItaly
  2. 2.Molecular and Nutritional Epidemiology UnitCancer Research and Prevention Institute (ISPO)FlorenceItaly
  3. 3.Division of Pathological Anatomy, Department of Medical and Surgical Critical CareUniversity of FlorenceFlorenceItaly
  4. 4.Unit of Medical Genetics, Department of Preventive and Predictive MedicineFondazione IRCCS, Istituto Nazionale dei TumoriMilanItaly
  5. 5.Division of Cancer Prevention and GeneticsIstituto Europeo di OncologiaMilanItaly
  6. 6.Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive MedicineFondazione IRCCS Istituto Nazionale Tumori (INT), and Fondazione Istituto FIRC di Oncologia Molecolare (IFOM)MilanItaly
  7. 7.F. Spaziani HospitalFrosinoneItaly
  8. 8.Unit of Hereditary CancersIstituto Nazionale per la Ricerca sul CancroGenoaItaly
  9. 9.Clinical Experimental Oncology LaboratoryNational Cancer Centre of BariBariItaly
  10. 10.Section of Medical Oncology, Department of Surgical and Oncological SciencesUniversity of PalermoPalermoItaly
  11. 11.Department of Oncology and HaematologyUniversity of Modena and Reggio EmiliaModenaItaly
  12. 12.Unit of Experimental Oncology ICentro di Riferimento Oncologico, IRCCSAvianoItaly
  13. 13.Immunology and Molecular Oncology UnitIstituto Oncologico Veneto, IRCCSPaduaItaly

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