title: Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy.
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.
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161 Rome, Italy. laura.ottini@uniroma1.it
authors.forename: L
authors.initials: L
authors.lastname: Ottini
authors.forename: V
authors.initials: V
authors.lastname: Silvestri
authors.forename: C
authors.initials: C
authors.lastname: Saieva
authors.forename: P
authors.initials: P
authors.lastname: Rizzolo
authors.forename: I
authors.initials: I
authors.lastname: Zanna
authors.forename: M
authors.initials: M
authors.lastname: Falchetti
authors.forename: G
authors.initials: G
authors.lastname: Masala
authors.forename: A S
authors.initials: AS
authors.lastname: Navazio
authors.forename: V
authors.initials: V
authors.lastname: Graziano
authors.forename: S
authors.initials: S
authors.lastname: Bianchi
authors.forename: S
authors.initials: S
authors.lastname: Manoukian
authors.forename: M
authors.initials: M
authors.lastname: Barile
authors.forename: P
authors.initials: P
authors.lastname: Peterlongo
authors.forename: C
authors.initials: C
authors.lastname: D'Amico
authors.forename: L
authors.initials: L
authors.lastname: Varesco
authors.forename: S
authors.initials: S
authors.lastname: Tommasi
authors.forename: A
authors.initials: A
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Giannini
authors.forename: L
authors.initials: L
authors.lastname: Cortesi
authors.forename: A
authors.initials: A
authors.lastname: Viel
authors.forename: M
authors.initials: M
authors.lastname: Montagna
authors.forename: P
authors.initials: P
authors.lastname: Radice
authors.forename: D
authors.initials: D
authors.lastname: Palli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D051017:Apoptosis Regulatory Proteins; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006609:High Mobility Group Proteins; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics; D015534:Trans-Activators
chemical_list: D051017:Apoptosis Regulatory Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D006609:High Mobility Group Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2