Background: Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens and environmental carcinogens. SULT1A1 Arg213His (638G>A) is a common functional polymorphism. The less functional 213His allele is associated with high levels of estrogens and with increased breast cancer risk, particularly in postmenopausal women. Male breast cancer (MBC) is an uncommon and poorly understood disease. Genetic and environmental factors are involved in the pathogenesis of MBC. As with females, hormonal factors, particularly high estrogen levels, are known to play a key role in MBC pathogenesis. Given the role of SULT1A1 Arg213His polymorphism in the metabolism of estrogens, we hypothesized that SULT1A1 genotype could exert some potential effect on MBC development. Materials and Methods: To investigate associations between this polymorphism and risk of MBC, we performed a two-stage case–control genetic association study. A total of 394 MBC cases and 786 healthy male controls were genotyped for the SULT1A1 Arg213His polymorphism. All MBC cases were characterized for BRCA1/2 mutations and for relevant clinical-pathologic features. SULT1A1 Arg213His genotyping was performed by PCR-RFLP and HRM analysis. Logistic regression models were applied to evaluate SNP-level associations. Results: A statistically significant difference in the distribution of the three specific SULT1A1 Arg213His genotypes was found between MBC cases and controls. The analysis of the genotype-specific risk showed that individuals with G/A and A/A genotypes were at increased MBC risk (OR = 1.86, 95% CI: 1.51– 2.31; P <0.0001). Furthermore, a statistically significant association emerged between A/A genotype and HER2 positive tumors (P <0.0007). Conclusions: Overall, our results indicate that SULT1A1 Arg213His may act as a low-penetrance risk allele for developing BC in men and that it could be associated with a specific tumor subtype. Study supported by AIRC (IG 12780) to L. O No conflict of interest.
962: Association of SULT1A1 Arg213His polymorphism with male breast cancer risk: a case−control study in Italy / Rizzolo, P.; Silvestri, V.; Giannini, G.; Varesco, L.; Viel, A.; Cortesi, L.; Montagna, M.; Radice, P.; Palli, D.; Ottini, L.. - In: EUROPEAN JOURNAL OF CANCER. - ISSN 0959-8049. - 50:(2014), pp. S234-S235. (Intervento presentato al convegno 23rd Biennal Congress of the European Association for Cancer Research tenutosi a Monaco di Baviera) [10.1016/S0959-8049(14)50854-4].
962: Association of SULT1A1 Arg213His polymorphism with male breast cancer risk: a case−control study in Italy
Rizzolo, P.;Silvestri, V.;Giannini, G.;Ottini, L.
2014
Abstract
Background: Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens and environmental carcinogens. SULT1A1 Arg213His (638G>A) is a common functional polymorphism. The less functional 213His allele is associated with high levels of estrogens and with increased breast cancer risk, particularly in postmenopausal women. Male breast cancer (MBC) is an uncommon and poorly understood disease. Genetic and environmental factors are involved in the pathogenesis of MBC. As with females, hormonal factors, particularly high estrogen levels, are known to play a key role in MBC pathogenesis. Given the role of SULT1A1 Arg213His polymorphism in the metabolism of estrogens, we hypothesized that SULT1A1 genotype could exert some potential effect on MBC development. Materials and Methods: To investigate associations between this polymorphism and risk of MBC, we performed a two-stage case–control genetic association study. A total of 394 MBC cases and 786 healthy male controls were genotyped for the SULT1A1 Arg213His polymorphism. All MBC cases were characterized for BRCA1/2 mutations and for relevant clinical-pathologic features. SULT1A1 Arg213His genotyping was performed by PCR-RFLP and HRM analysis. Logistic regression models were applied to evaluate SNP-level associations. Results: A statistically significant difference in the distribution of the three specific SULT1A1 Arg213His genotypes was found between MBC cases and controls. The analysis of the genotype-specific risk showed that individuals with G/A and A/A genotypes were at increased MBC risk (OR = 1.86, 95% CI: 1.51– 2.31; P <0.0001). Furthermore, a statistically significant association emerged between A/A genotype and HER2 positive tumors (P <0.0007). Conclusions: Overall, our results indicate that SULT1A1 Arg213His may act as a low-penetrance risk allele for developing BC in men and that it could be associated with a specific tumor subtype. Study supported by AIRC (IG 12780) to L. O No conflict of interest.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
