Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil.

Introduction Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research. Objective To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages. Methods A set of 17 genes ( BRCA1 , BRCA2 , APC , TP53 , PTEN , RET , VHL , RB1 , CDKN2 , CDH1 , CHEK2 , MLH1 , MSH2 , MSH6 , MUTYH , XPA , and XPC ) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated. Results The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure. Conclusion The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.

Fertirrigação do milho com água residuária sanitária tratada: crescimento e produção / Maize fertigation with treated sanitary wastewater: growth and yield

RESUMO Avaliou-se o crescimento vegetativo e a produção de milho em campo, fertirrigado com diferentes doses de água residuária da estação de tratamento de esgoto de Janaúba, Minas Gerais. Utilizou-se o delineamento em quatro blocos casualizados com parcelas subdivididas, sendo cinco tratamentos: água limpa + adubação mineral; e água residuária tratada equivalente a 50; 100; 150 e 200% da adubação com 60 kg.ha-1 de K2O em cobertura. Nas subparcelas, avaliaram-se as plantas aos 24, 38, 51 e 74 dias após a emergência. O fornecimento de doses de potássio via água residuária tratada além de 142% da dose recomendada do nutriente reduz o diâmetro transversal da copa. A produtividade do milho em grãos não é influenciada pela aplicação de água residuária tratada.

ABSTRACT We evaluated the growth and yield of maize field, fertigated with different wastewater rates coming from Janaúba sewage treatment plant (Minas Gerais State, Brazil). The split-plot on a randomized complete block design was used with five levels: mineral fertilizer + clean water, treated wastewater like to 50%, 100%, 150% and 200% fertilization with 60 kg.ha-1 K2O topdressing. As subplots, maize plants were evaluated at 24, 38, 51 and 74 days after emergence. Potassium supply 142% above the recommended level decrease the transversal canopy diameter. Maize grain yield is not affected by wastewater fertigation.

Avaliação de danos genéticos e apoptose em mulheres menopausadas que fazem uso da terapia de reposição hormonal / Assessment of genetic damage and apoptosis in postmenopausal women under hormone replacement therapy

Objetivo: Avaliar por meio do teste de micronúcleo em células esfoliadas da mucosa oral a genotoxicidade de hormônios empregados na terapia de reposição hormonal (TRH). Material e métodos: Quarenta mulheres menopausadas foram selecionadas e distribuídas em quatro grupos de dez: G0 (não submetidas à TRH), G1 (TRH com estrógeno), G2 (TRH com estrógeno e progestágeno) e G3 (TRH com tibolona). Células esfoliadas da mucosa oral foram coletadas e processadas para análise, sob microscopia óptica, de danos cromossômicos (micronúcleos) e de apoptose, inferida pelo somatório de alterações nucleares degenerativas (picnose, cariorréxis e cromatina condensada). Duas mil células foram analisadas por participante. A análise estatística foi feita com o uso do teste condicional para comparação de proporções em situação de eventos raros. Resultados: A frequência de micronúcleo não diferiu entre os grupos (p > 0,05). As alterações nucleares indicativas de apoptose foram significativamente mais altas entre as mulheres do G0 em relação às dos demais grupos (p < 0,01). Os grupos submetidos à TRH não diferiram quanto à ocorrência de apoptose (p > 0,05). Conclusões: Esses resultados indicam que, tal como avaliado neste estudo, a TRH não induz danos cromossômicos. Entretanto, devido ao efeito antiapoptótico, permite a proliferação de células geneticamente danificadas, está assim potencialmente associada ao processo de transformação maligna.(AU)

Objective: To evaluate through the micronucleus test in exfoliated cells of oral mucosa the genotoxicity of hormones used in hormone replacement therapy (HRT). Material and methods: Forty postmenopausal women were selected and divided into four groups of ten: G0 (not submitted to HRT), G1 (HRT with estrogen), G2 (HRT with estrogen and progestogen) and G3 (HRT with tibolone). Exfoliated cells of oral mucosa were collected and processed for analysis of chromosomal damage (micronuclei) and apoptosis, inferred by the sum of nuclear degenerative alterations (picnosis, cariorréxis and condensed chromatin). Two thousand cells were analyzed by participant. Statistical analysis was performed using the conditional test to compare proportions in a situation of rare events. Results: The frequency of micronuclei did not differ between groups (p > 0.05). Apoptotic cells were significantly higher among women from G0 when compared to the other groups (p < 0.01). The groups submitted to HRT did not differ in apoptosis occurrence (p > 0.05). Conclusions: These results indicate that, as assessed in this study, TRH does not induce chromosomal damage, however, due to the anti-apoptotic effect, cells genetically damaged can proliferate, favoring the malignant transformation process.(AU)

Germline mutations in BRCA1, BRCA2, CHEK2 and TP53 in patients at high-risk for HBOC: characterizing a Northeast Brazilian Population.

Considering the importance of BRCA1, BRCA2, CHEK2 and TP53 in the development of hereditary early-onset breast and ovarian cancer and that the genetic susceptibility profile of the Northeast population from Brazil has never been analyzed, this study aimed to verify the frequency of mutations of clinical significance in these genes in high-risk hereditary breast and ovarian cancer (HBOC) syndrome patients from that region. DNA samples from 106 high-risk unrelated patients mostly from Bahia, the biggest state in the Northeast region, were analyzed. These patients underwent full BRCA1 gene sequencing, screening for common founder mutations in the BRCA2, CHEK2 and TP53 genes and genetic ancestry analysis with nine ancestry informative markers. The positive results were confirmed by two sequencing reactions. Three mutations of clinical significance were found: BRCA1 p.R71G (4.71%), 3450del4 (3.77%) and TP53 p.R337H (0.94%). The genetic ancestry analysis showed a high European ancestry contribution (62.2%) as well as considerable African (31.2%) and Amerindian (6.6%) ancestry contributions (r (2)=0.991); this degree of heterogeneity was also significant in the population structure analysis (r=0.604). This population is highly admixed with a different spectrum of genetic susceptibility, with the Galician founder mutation BRCA1 p.R71G accounting for 50% of all identified mutations in high-risk HBOC patients. TP53 p.R337H was also significantly frequent; thus, the combined screening of BRCA1/2 and TP53 should be offered to high-risk HBOC patients from Northeast Brazil.

Ancestralidade genética e genes de susceptibilidade em portadores de câncer de próstata do Estado da Bahia / Genetic ancestry and susceptibility genes in patients with prostate cancer of Bahia

O Cancêr de Próstata (CaP) é um dos tipos de neoplasias mais frequentes nos homens em todo o mundo e também na população masculina brasileira. A incidência, mortalidade e agressividade do CaP são maiores em homens negros. De acordo com o IBGE a Bahia é o estado que apresenta a maior porcentagem de população afrodescendente e os indivíduos que moram em Salvador apresentam maior ancestralidade africana que os nascidos no interior do estado. O presente estudo verificou a associação entre maior ancestralidade genética africana e genes de suscetibilidade ao CaP em pacientes do estado da Bahia oriundos do setor particular e público de serviço à saúde. Participaram do estudo 189 homens com CaP, sendo 82 atendidos no serviço privado e 107 no serviço público e 112 homens saudáveis atendidos no serviço público. Foram utilizados 9 marcadores informativos de ancestralidade (AIM) para estimar a ancestralidade genética e quatro genes de suscetibilidade: CYP3A4, CYP17, GSTM1 e GSTT1...

Prostate cancer (PCa) is one of the most common types of cancer in men worldwide and also in Brazilian male population. The incidence, mortality and PCa aggressiveness are higher in black men. According to the IBGE, Bahia is the state with the highest percentage of people of African descent and people who live in Salvador has the largest African ancestry born in the state. The present study sought to determine the association between African ancestry and greater susceptibility genes in PCa patients of Bahia state from public and private sector health service. The study included 189 men with PCa, 82 served in the private and 107 public service and 112 healthy men served in the public service. We used ancestry informative markers 9 (AIM) to estimate genetic ancestry and 4 susceptibility genes, among them: CYP3A4, CYP17, GSTM1 e GSTT1...