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Nat Commun ; 10(1): 1741, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988301


Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Neoplasias da Mama/genética , Predisposição Genética para Doença , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas
Magn Reson Imaging ; 59: 77-87, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30880110


OBJECTIVES: To investigate the feasibility of chemical exchange saturation transfer (CEST) MRI in patients with breast carcinomas and possible correlations between magnetization transfer asymmetry (MTRasym) values and histological features, such as tumor grade and the Ki-67 proliferation index. MATERIALS AND METHODS: Nine healthy subjects and 18 female patients were enrolled for this study. The imaging protocol for the patients consisted of diffusion-weighted imaging (DWI), CEST imaging, and T1-weighted, contrast-enhanced (CE)-MRI. CEST was performed using a 3D gradient echo (GRE) sequence, employing eight pre-saturation pulses of a duration of 50 ms and a duty cycle (DC) of 80%, with a mean amplitude of the saturation pulse train of 1 µT. The Z-spectrum was plotted and MTRasym values calculated for the frequency of the maximum of MTRasym curve, were correlated with the Ki-67 proliferation index and apparent diffusion coefficient (ADC). Patient data were statistically assessed using the Games-Howell post-hoc and Pearson's correlation test. RESULTS: Different tumor types had asymmetry peaks at different positions of Z-spectrum. MTRasym (mean ±â€¯SD) (%) calculated for G1 (3.0 ±â€¯0.3; range: 2.70-3.50) was not significantly lower than for G2 (4.50 ±â€¯1.30; range: 3.20-6.50; p = 0.066). In contrast, the increase in MTRasym between G1 and G3 (6.40 ±â€¯1.70; range: 4.80-9.80) lesions was significant (p = 0.007). No significant difference was observed between G2 and G3 with regard to MTRasym (p = 0.089). There was a strong positive correlation between the MTRasym, and Ki-67 proliferation index (r = 0.890; p = 0.001), while there was a moderate negative correlation between MTRasym and ADC values (r = -0.506; p = 0.027). CONCLUSIONS: Calculated MTRasym demonstrates a strong positive correlation with tumor proliferation and has the potential to become a valuable biomarker for breast tumor characterization.

Tecido Adiposo/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Imagem por Ressonância Magnética , Gradação de Tumores , Adulto , Biomarcadores , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
PLoS One ; 13(7): e0200559, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30001421


OBJECTIVE: Genetic counseling and testing can be offered to individuals who are at high risk of carrying a breast cancer (BRCA) gene mutation. However, the content of genetic counseling could be difficult to understand due to complex medical information. The aim of this study was to investigate if comprehension can be improved with a new genetic counseling tool (NGCT hereafter; a tool that combines complex medical information with pictures, diagrams and tables) as compared to conventional oral-only genetic counseling (CGC). METHODS: 207 clients attended genetic counseling for hereditary breast and ovarian cancer at the Medical University of Vienna between February 2015 and February 2016. Seventy clients participated in this study and were allocated into two groups: the first 36 participants received conventional (oral only) genetic counseling (CGC) and the following 34 participants received genetic counseling using a new genetic counseling tool (NGCT), which combines complex information with pictures, diagrams and tables. After genetic counseling, all consenting participants were invited to complete a questionnaire with seven questions evaluating their comprehension of the medical information provided. RESULTS: Socio-demographic backgrounds were comparable in both groups. Correct responses were significantly higher in the NGCT group compared to the CGC group (p = 0.012). NGCT also statistically improves correct response of Q1 (p = 0.03) and Q7 (p = 0.004). CONCLUSION: The NGCT leads to an overall better understanding of the content of a genetic counseling session than CGC alone.

Hum Mutat ; 39(5): 593-620, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29446198


The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

Pediatr Surg Int ; 25(1): 73-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18985359


PURPOSE: Breast diseases in teenage girls are fortunately uncommon, with most presenting masses being benign. The aim of this study was to evaluate the histopathological results of breast lesions excised from adolescent females less than 19 years of age. METHODS: The authors reviewed the medical and pathology records at the University Hospital of Vienna, Department of Obstetrics and Gynaecology, between 1993 and 2006, retrospectively. All data included the patient age, age of menarche, pregnancy, hormonal contraception, family history of breast cancer, size of the breast lesion and its histopathology following surgery. RESULTS: Thirty-seven female patients with an average age of 16 years (ranging 12-18 years) were operated on for breast tumor and/or discharge. All tumors were palpable. Six patients had bilateral breast masses; thus, 43 breast lesions were evaluated following surgical excision. Surprisingly, breast cancer was found in two cases. Both patients were diagnosed with a noninvasive ductal carcinoma in situ (DCIS) within a fibroadenoma at the age of 16. These are the first reported cases of DCIS found in this young age group. As breast neoplasm was found in two cases, a malignancy rate of 4.7% was observed. The most common histologies were fibroadenoma (n=27) and fibrocystic disease (n=4). CONCLUSION: The incidence of primary breast cancer in adolescent women is low. However, our experience shows the need for compulsory excision of all breast masses and highlighting the importance of histopathological evaluation of all breast tumors including adolescents.

Neoplasias da Mama/patologia , Doença da Mama Fibrocística/patologia , Adolescente , Áustria , Neoplasias da Mama/cirurgia , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Criança , Feminino , Fibroadenoma/patologia , Fibroadenoma/cirurgia , Doença da Mama Fibrocística/cirurgia , Predisposição Genética para Doença , Humanos , Mastectomia , Tumor Filoide/patologia , Tumor Filoide/cirurgia , Estudos Retrospectivos