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Breast Cancer Research and Treatment

, Volume 148, Issue 3, pp 623–628 | Cite as

Association of SULT1A1 Arg213His polymorphism with male breast cancer risk: results from a multicenter study in Italy

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

Abstract

Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg213His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg213His could exert an effect on MBC development. The primary aim of this study was to evaluate the influence of the SULT1A1 Arg213His polymorphism on MBC risk. The secondary aim was to investigate possible associations with relevant clinical–pathologic features of MBC. A total of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1 Arg213His polymorphism by PCR–RFLP and high-resolution melting analysis. All MBC cases were characterized for relevant clinical–pathologic features. A significant difference in the distribution of SULT1A1 Arg213His genotypes was found between MBC cases and controls (P < 0.0001). The analysis of genotype-specific risk showed a significant increased MBC risk in individuals with G/A (OR 1.97, 95 % CI 1.50–2.59; P < 0.0001) and A/A (OR 3.09, 95 % CI 1.83–5.23; P < 0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A significant association between SULT1A1 risk genotypes and HER2 status emerged. Results indicate that SULT1A1 Arg213His may act as a low-penetrance risk allele for developing MBC and could be associated with a specific tumor subtype associated with HER2 overexpression.

Keywords

Male breast cancer Estrogens Estrogen receptor Sulfotransferase 1A1 (SULT1A1) SULT1A1 Arg213His polymorphism 

Notes

Acknowledgments

The authors wish to thank Lesley Pritikin for her assistance with preparation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by AIRC (Associazione Italiana Ricerca Cancro, Grant No. IG12780) to L.O., FIRC (Fondazione Italiana Ricerca Cancro triennial fellowship “Mario e Valeria Rindi”) to V.S., and ITT (Istituto Tumori Toscano, triennial Grant 2010, Grant No. 6204) to D.P.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • L. Ottini
    • 1
  • P. Rizzolo
    • 1
  • I. Zanna
    • 2
  • V. Silvestri
    • 1
  • C. Saieva
    • 2
  • M. Falchetti
    • 1
  • G. Masala
    • 2
  • A. S. Navazio
    • 1
  • C. Capalbo
    • 1
  • S. Bianchi
    • 3
  • S. Manoukian
    • 4
  • M. Barile
    • 5
  • P. Peterlongo
    • 6
    • 7
  • M. A. Caligo
    • 8
  • L. Varesco
    • 9
  • S. Tommasi
    • 10
  • A. Russo
    • 11
  • G. Giannini
    • 1
  • L. Cortesi
    • 12
  • G. Cini
    • 13
  • M. Montagna
    • 14
  • P. Radice
    • 6
    • 7
  • 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 dei Tumori (INT)MilanItaly
  7. 7.Fondazione Istituto FIRC di Oncologia MolecolareMilanItaly
  8. 8.Section of Genetic OncologyUniversity of PisaPisaItaly
  9. 9.Unit of Hereditary CancersIRCCS AOU San Martino – ISTGenoaItaly
  10. 10.Clinical Experimental Oncology LaboratoryNational Cancer Centre of BariBariItaly
  11. 11.Section of Medical Oncology, Department of Surgical and Oncological SciencesUniversity of PalermoPalermoItaly
  12. 12.Department of Oncology and HaematologyUniversity of Modena and Reggio EmiliaModenaItaly
  13. 13.CRO Aviano National Cancer InstituteAvianoItaly
  14. 14.Immunology and Molecular Oncology UnitIstituto Oncologico Veneto, IRCCSPaduaItaly

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