The Brazilian TP53 mutation (R337H) and sarcomas Volc, Sahlua Miguel; Ramos, Cíntia Regina Niederauer; Galvão, Henrique de Campos Reis ...
PloS one,
01/2020, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Open access
Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is ...central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.
To evaluate the association of dietary inflammatory index (DII®) with the occurrence of cardiovascular events, cardiometabolic risk factors and with the consumption of processed, ultra-processed, ...unprocessed or minimally processed foods and culinary ingredients.
This was a cross-sectional study that analysed the baseline data from 2359 cardiac patients. Data on socio-demographic, anthropometric, clinical and food consumption were collected. Energy-adjusted food intake data were used to calculate DII, and the foods were classified according to the NOVA classification. Furthermore, the patients were grouped according to the number (1, 2 or ≥ 3) of manifested cardiovascular events. The data were analysed using linear and multinomial logistic regression.
Multicentre study from Brazil.
Patients with established cardiovascular events from the Brazilian Cardioprotective Nutritional Program Trial evaluated at baseline.
Most of the patients were male (58·8 %), older adults (64·2 %) and were overweight (68·8 %). Patients in the third tertile of DII (DII > 0·91) had were more likely to have 2 (OR 1·27, 95 % CI: 1·01-1·61) and ≥ 3 (OR 1·39, 95 % CI: 1·07-1·79) cardiovascular events, with poor cardiometabolic profile. They also were more likely to consume a higher percentage of processed, ultra-processed and culinary ingredients foods consumption compared with the patients in the first DII tertile (DII ≤ 0·91).
A more pro-inflammatory diet is associated with a greater chance of having 2 and ≥ 3 cardiovascular events and cardiometabolic risk factors and were more likely to consume processed, ultra-processed and culinary ingredients compared to those with a more anti-inflammatory diet.
The use of gene panels introduces a new dilemma in the genetics field due to the high frequency of variants of uncertain significance (VUS). The objective of this study was to provide evidence that ...may help in the classification of these germline variants in terms of their clinical impact and association with the disease in question. A total of 52 unrelated women at-risk for HBOC and negative for
BRCA1/BRCA2
pathogenic variants were evaluated through a gene panel comprising 14 breast and/or ovarian cancer susceptibility genes. Of the 453 germline variants identified, 15 variants (classes 3, 4, and 5) in the
ATM, BRIP1, CHEK2, MRE11A, MUTHY, PALB2, RAD50
, and
RAD51C
genes were evaluated via databases, co-segregation studies and loss of heterozygosity in the tumor. The co-segregation analysis allowed the establishment of an association with the presence of variants and the risk of cancer for variant c.316C>T in the
BRIP1
gene. Four variants of uncertain significance showed loss of heterozygosity in the tumor (
ATM
c.4709T>C;
CHEK2
c.1036C>T;
PALB2
c.1001A>G, and
RAD50
c.281T>C), which is an indication of pathogenicity. Thus, the present study provides novel evidence that favors the association of variants in moderate-risk genes with the development of hereditary breast cancer.
Specific pathogenic mutations associated with breast cancer development can vary between ethnical groups. One example is BRCA1 c.5266dupC that was first described as a founder mutation in the ...Ashkenazi Jewish population, but was later also found in other populations. In Brazil, this mutation corresponds to 20% of pathogenic BRCA1 variants reported. Our objective was to investigate the haplotype component of a group of Brazilian families who inherited c.5266dupC in the BRCA1 gene and to verify the ancestry contribution from European, African, and Amerindian origins. Fourteen probands carrying c.5266dupC and 16 relatives (carriers and non-carriers) were investigated. The same haplotype was observed segregating within all the families analyzed, revealing no recombinants in a region of 0.68 Mb. Ancestry analysis demonstrated that the European component was predominant among probands. The BRCA1 c.5266dupC analysis indicates that there was a founder effect in the Brazilian population.
The consumption of ultra-processed foods (UPF) has been associated with cardiometabolic risk factors. However, there is scarce literature on the association between UPF consumption, cardiovascular ...events, and cardiometabolic risk factors in subjects undergoing secondary care for cardiovascular diseases (CVD). Thus, we aimed to evaluate the association between UPF consumption, CVD, and cardiometabolic risk factors in subjects with established CVD. Baseline data from 2,357 subjects participating in a Brazilian multicenter study were analysed finding a mean UPF consumption of 18.7% of their energy intake. Higher figures of UPF consumption were founded associated with an increased presence of high waist circumference, overweight, peripheral arterial disease, and with a decreased odds of the simultaneous presence of coronary arterial disease, peripheral arterial diseases, and stroke when comparing among tertiles of UPF contribution to energy intake. These associations were observed when analyzing the whole sample and women but not men. Thus, these findings should help improve strategies for CVD patients in secondary care.
The identification of families at-risk for hereditary breast cancer (BC) is important because affected individuals
present a much higher cancer risk than the general population. The aim of this study ...was to identify the most important
factors associated with the presence of a pathogenic BRCA1/BRCA2 mutation. Family history (FH), histopathological
and immunohistochemical characteristics were compared among BC women with pathogenic BRCA1/BRCA2 variants;
VUSs in BRCA1/BRCA2; BRCA1/BRCA2 WT and sporadic BC. The most significative differences observed concerned
the molecular subtype of the tumors, age at cancer diagnosis and FH of cancer. The presence of bilateral breast cancer
(BBC), number of BC cases and the presence of ovarian cancer (OC) increased (respectively) 5.797, 5.033 and 4.412
times the risk of being a BRCA1/BRCA2 mutation carrier. Besides, women with BRCA1 or BRCA2 mutations presented
different tumor and FH profiles. The main characteristics associated with a BRCA1 mutation were triple negativity
(OR: 17.31), BBC history (OR: 4.96) and occurrence of OC (OR: 4.32). There were no major discerning components
associated with BRCA2 mutations. Thus, we conclude that tumor pathology and FH of cancer might be considered
together at the time of genetic testing mainly in countries where access to genetic testing is still restricted.
The Brazilian TP53 mutation Volc, Sahlua Miguel; Ramos, Cíntia Regina Niederauer; Galvão, Henrique de Campos Reis ...
PloS one,
01/2020, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is ...central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.
Abstract Introduction: Postural control is a multidimensional construct modulated by the integration of sensory information and muscular activity. One of the challenges in clinical practice and ...scientific research is the postural data collection of objective control data. Thus, baropodometry can be a promising instrument for analysis. Objective: To evaluate the absolute and relative reliability of baropodometry by means of test-retest in young asymptomatic subjects during semi-static and dynamic analysis. Methods: This is a methodological study, approved by the Research Ethics Committee of UFJF (1,803,411). Sample selection was performed by convenience. Healthy individuals aged 18 to 35 years were included in the study without gender restriction. Participants with pain or any clinical signs of overload which led to unfeasible collection were excluded from the analysis. The variables analyzed were contact surface, maximum and mean pressure, index bow, pressure center and pressure areas in the forefoot, midfoot and hindfoot. Results: 33 individuals (total of 66 feet) participated in this study. The mean body mass of the participants was 63.0 ± 9.9kg, height of 163.4 ± 30.1cm, BMI of 23.7 ± 2.8 kg/m2. It was observed that five out of the eight variables evaluated in the semi-static analysis presented high reliability (≥ 0.70). On the other hand, the reproducibility of the measures in the dynamic analysis was low to moderate (≤ 0.69). Conclusion: Baropodometry findings should be interpreted with caution in clinical practice and in scientific research. It is suggested that complementary assessments be made for decision-making assistance.
Resumo Introdução: O controle postural é um constructo multidimensional modulado pela integração de informações sensoriais e atividade muscular. Um dos desafios na prática clínica e em pesquisas científicas é a obtenção de dados objetivos do controle postural. Baseando-se nessa premissa, a baropodometria pode ser um instrumento promissor para esta análise. Objetivo: Avaliar a confiabilidade absoluta e relativa por meio de teste-reteste da baropodometria em indivíduos jovens assintomáticos durante análise semi estática e dinâmica. Métodos: Trata-se de um estudo metodológico, aprovado pelo Comitê de Ética em pesquisa da UFJF (parecer 1.803.411). A seleção da amostra foi por conveniência. Foram incluídos indivíduos hígidos de 18 a 35 anos sem restrição de gênero e excluídos participantes com queixa álgica ou qualquer sinal clínico de sobrecarga que inviabilizasse a coleta. As variáveis analisadas foram superfície de contato, pressão máxima e média, arco index, centro de pressão e as áreas de pressão no antepé, mediopé e retropé. Resultados: Participaram do estudo 33 indivíduos (66 pés). A média de massa corporal dos participantes foi de 63,0 ± 9,9 kg, estatura de 163,4 ± 30,1 cm, IMC de 23,7 ± 2,8 kg/m2 e número do calçado 38,0 ± 2,1. Observamos que das oito variáveis avaliadas na análise semi estática, cinco apresentaram confiabilidade alta (CCI ≥ 0.70). Por outro lado, a reprodutibilidade das medidas na análise dinâmica foi de baixa à moderada (CCI ≤ 0.69). Conclusão: Os achados da baropodometria devem ser interpretados com cautela na prática clínica e em pesquisa científica. Sugere-se que sejam realizadas avaliações complementares para o auxílio de tomada de decisões.
About 5-10% of breast/ovarian cancers are hereditary. However, for a large proportion of cases (around 50%), the genetic cause remains unknown. These cases are grouped in a separated BRCAX category. ...The aim of this study was to identify genomic alterations in
wild-type tumor samples from women with family history strongly suggestive of hereditary breast/ovarian cancer.
A cohort of 31 Brazilian women was included in the study. Using the GISTIC algorithm, we identified 20 regions with genomic gains and 31 with losses. The most frequent altered regions were 1q21.2, 6p22.1 and 8p23.3 in breast tumors and Xq26 and Xp22.32-22.31 among the ovarian cancer cases. An interesting association identified was the loss of 22q13.31-13.32 and the presence of ovarian cancer cases. Among the genes present in the frequently altered regions, we found
,
,
,
,
,
,
and several genes of
and
family.
In conclusion, our results suggest that alterations on chromosomes 1, 6, 8 and X are common on BRCAX tumors and that the loss on 22q can be associated with the presence of ovarian cancer.
DNA copy number alterations were analyzed by 60K array comparative genomic hybridization in breast and ovarian FFPE tumors.
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