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

  • 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.

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Acknowledgments

The study was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC IG 8713).

Conflict of interest

  The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    L. Ottini, V. Silvestri, P. Rizzolo, M. Falchetti, A. S. Navazio, V. Graziano & G. Giannini

  2. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy

    C. Saieva, I. Zanna, G. Masala & D. Palli

  3. Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    S. Bianchi

  4. Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy

    S. Manoukian

  5. Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy

    M. Barile

  6. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), and Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy

    P. Peterlongo & P. Radice

  7. F. Spaziani Hospital, Frosinone, Italy

    C. D’Amico

  8. Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

    L. Varesco

  9. Clinical Experimental Oncology Laboratory, National Cancer Centre of Bari, Bari, Italy

    S. Tommasi

  10. Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy

    A. Russo

  11. Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy

    L. Cortesi

  12. Unit of Experimental Oncology I, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy

    A. Viel

  13. Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto, IRCCS, Padua, Italy

    M. Montagna

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  1. L. Ottini
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  2. V. Silvestri
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  8. A. S. Navazio
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  9. V. Graziano
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  10. S. Bianchi
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  14. C. D’Amico
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  15. L. Varesco
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  16. S. Tommasi
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  17. A. Russo
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  18. G. Giannini
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  22. P. Radice
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Correspondence to L. Ottini.

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Ottini, L., Silvestri, V., Saieva, C. et al. Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy. Breast Cancer Res Treat 138, 861–868 (2013). https://doi.org/10.1007/s10549-013-2459-4

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  • DOI: https://doi.org/10.1007/s10549-013-2459-4

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