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01.12.2014 | Epidemiology | Ausgabe 3/2014

Breast Cancer Research and Treatment 3/2014

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

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 3/2014
Autoren:
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

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.

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