title: SULT1A1 gene deletion in BRCA2-associated male breast cancer: a link between genes and environmental exposures?
abstract: SULT1A1, a member of sulfotransferase superfamily, is a drug and hormone metabolizing enzyme involved in the metabolism of a variety of potential mammary carcinogens of endogenous and exogenous origin. Interestingly, the metabolic activity of SULT1A1 can be affected by variations in gene copy number. Male Breast Cancer (MBC) is a rare disease and less investigated disease compared to female BC (FBC). As in FBC, the concurrent effects of genetic risk factors, particularly BRCA2 mutations, increased exposure to estrogens and environmental carcinogens play a relevant role in MBC. By quantitative real-time PCR with TaqMan probes, we investigated the presence of SULT1A1 gene copy number variations (CNVs) in a series of 72 MBCs. SULT1A1 gene deletion was observed in 10 of the 72 MBCs (13.9%). In a multivariate analysis association between BRCA2 mutation and SULT1A1 gene deletion emerged (p = 0.0005). Based on the evidence that the level of SULT1A1 enzyme activity is correlated with CNV, our data suggest that in male breast tumors SULT1A1 activity may be decreased. Thus, it can be hypothesized that in a proportion of MBCs, particularly in BRCA2-associated MBCs, the level of estrogens and environmental carcinogens exposure might be increased suggesting a link between gene and environmental exposure in the pathogenesis of MBC.
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Piera
authors.initials: P
authors.lastname: Rizzolo
authors.forename: Ines
authors.initials: I
authors.lastname: Zanna
authors.forename: Valentina
authors.initials: V
authors.lastname: Silvestri
authors.forename: Calogero
authors.initials: C
authors.lastname: Saieva
authors.forename: Mario
authors.initials: M
authors.lastname: Falchetti
authors.forename: Anna Sara
authors.initials: AS
authors.lastname: Navazio
authors.forename: Veronica
authors.initials: V
authors.lastname: Graziano
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
mesh_terms: D015239:Arylsulfotransferase / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000473:pathology; D004781:Environmental Exposure; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human