Abstract Admixed populations have not been examined in detail in cancer genetic studies. Here, we inferred the local ancestry of cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes of a highly admixed Brazilian population. SNP array was used to genotype 73 unrelated individuals aged 80-102 years. Local ancestry inference was performed by merging genotyped regions with phase three data from the 1000 Genomes Project Consortium using RFmix. The average ancestry tract length was 9.12-81.71 megabases. Strong linkage disequilibrium was detected in 48 haplotypes containing 35 SNPs in 10 cancer driver genes. All together, 19 risk and eight protective alleles were identified in 23 out of 48 haplotypes. Homozygous individuals were mainly of European ancestry, whereas heterozygotes had at least one Native American and one African ancestry tract. Native-American ancestry for homozygous individuals with risk alleles for HNF1B, CDH1, and BRCA1 was inferred for the first time. Results indicated that analysis of SNP polymorphism in the present admixed population has a high potential to identify new ancestry-associated alleles and haplotypes that modify cancer susceptibility differentially in distinct human populations. Future case-control studies with populations with a complex history of admixture could help elucidate ancestry-associated biological differences in cancer incidence and therapeutic outcomes.

Resumo Esta revisão teve por objetivo comparar a literatura Latino-Americana sobre o conhecimento da neoplasia mamária e seus fatores de risco. Foram selecionados 47 estudos, dos quais 27 eram sobre o risco de desenvolver câncer de mama e 20 sobre o conhecimento ou a consciência sobre a doença. Os estudos sobre fatores de risco eram principalmente do tipo caso-controle e sua maioria estava no idioma Inglês. Já as pesquisas sobre conhecimento eram, sobretudo, do tipo transversal e foram publicadas nos idiomas Português e Espanhol. As pesquisas sobre conhecimento destacaram o diagnóstico precoce da neoplasia mamária, e o autoexame da mama foi o método de detecção mais abordado (N = 14). Por outro lado, os estudos sobre fatores de risco avaliaram, principalmente, sobrepeso (N = 14), historia familiar (N = 13), baixa paridade (N = 12) e curto período de amamentação (N = 10). Fatores socioeconômicos, como a renda e o nível educacional tiveram efeitos variáveis e afetaram também o conhecimento das mulheres sobre fatores de risco e detecção precoce. Os resultados da pesquisa indicaram que os estudos sobre fatores de risco do câncer de mama apresentaram melhor delineamento metodológico e fundamentação teórica, comparado com os estudos sobre conhecimento que foram na maioria dos casos descritivos.

Abstract The aim of this integrative review was to compare Latin American literature about risk and knowledge on breast cancer. Of 47 studies selected, 20 were about knowledge or awareness and 27 about risk of breast cancer. English was the dominant language in studies about risk, whereas studies about knowledge were mainly written in Spanish or Portuguese. Studies about knowledge were all cross- sectional, whereas case- control studies dominated authors’ interest about risk of breast cancer. Studies about knowledge were mainly focused on early detection of the disease and the most common study objective was breast self- examination (N = 14). In contrast, few studies about risk of breast cancer focused on early detection (N = 5). Obesity and overweight (N = 14), family history (N = 13), decreased parity (N = 12), and short breastfeeding duration (N = 10) were among the most frequent identified risk factors. Socio- economic factors such as income and educational level had variable effects on breast cancer risk and affected also knowledge of women about risk factors and early detection. Present results indicated that studies about risk of breast cancer were more often based on a better sound analytical background, compared to studies about knowledge, which were mostly descriptive.

Resumo Esta revisão teve por objetivo comparar a literatura Latino-Americana sobre o conhecimento da neoplasia mamária e seus fatores de risco. Foram selecionados 47 estudos, dos quais 27 eram sobre o risco de desenvolver câncer de mama e 20 sobre o conhecimento ou a consciência sobre a doença. Os estudos sobre fatores de risco eram principalmente do tipo caso-controle e sua maioria estava no idioma Inglês. Já as pesquisas sobre conhecimento eram, sobretudo, do tipo transversal e foram publicadas nos idiomas Português e Espanhol. As pesquisas sobre conhecimento destacaram o diagnóstico precoce da neoplasia mamária, e o autoexame da mama foi o método de detecção mais abordado (N = 14). Por outro lado, os estudos sobre fatores de risco avaliaram, principalmente, sobrepeso (N = 14), historia familiar (N = 13), baixa paridade (N = 12) e curto período de amamentação (N = 10). Fatores socioeconômicos, como a renda e o nível educacional tiveram efeitos variáveis e afetaram também o conhecimento das mulheres sobre fatores de risco e detecção precoce. Os resultados da pesquisa indicaram que os estudos sobre fatores de risco do câncer de mama apresentaram melhor delineamento metodológico e fundamentação teórica, comparado com os estudos sobre conhecimento que foram na maioria dos casos descritivos.

Abstract The aim of this integrative review was to compare Latin American literature about risk and knowledge on breast cancer. Of 47 studies selected, 20 were about knowledge or awareness and 27 about risk of breast cancer. English was the dominant language in studies about risk, whereas studies about knowledge were mainly written in Spanish or Portuguese. Studies about knowledge were all cross- sectional, whereas case- control studies dominated authors’ interest about risk of breast cancer. Studies about knowledge were mainly focused on early detection of the disease and the most common study objective was breast self- examination (N = 14). In contrast, few studies about risk of breast cancer focused on early detection (N = 5). Obesity and overweight (N = 14), family history (N = 13), decreased parity (N = 12), and short breastfeeding duration (N = 10) were among the most frequent identified risk factors. Socio- economic factors such as income and educational level had variable effects on breast cancer risk and affected also knowledge of women about risk factors and early detection. Present results indicated that studies about risk of breast cancer were more often based on a better sound analytical background, compared to studies about knowledge, which were mostly descriptive.

ResumoO atraso no tratamento de câncer de mama foi associado com o aumento do palco da doença e a diminuição da sobrevida do paciente. O objetivo desta revisão integrativa foi a analise dos principais fatores causais e dos tipos de atraso. Sendo estes comparados entre estudos de países em desenvolvimento e desenvolvidos. Dos 53 estudos selecionados, 24 eram de países em desenvolvimento e 29 de países desenvolvidos, respectivamente. A não atribuição dos sintomas ao câncer, o medo e a menor escolaridade foram as causas mais citadas do atraso de paciente ao tratamento. Seguro menos abrangente, idade e testes diagnósticos falsos negativos foram às causas mais comuns identificadas do atraso do sistema. O efeito de vários fatores como o fator idade, dependeu principalmente do contexto social e cultural. Alguns fatores causaram tanto atraso relacionado ao paciente quanto ao sistema. Os estudos dos países em desenvolvimento identificaram mais fatores causais do atraso relacionado ao paciente, focando mais forte neste referido fator ou na combinação com o de sistema. Enquanto estudos de países desenvolvidos enfocaram com maior frequência aspectos do atraso de sistema durante o tratamento e a orientação de pacientes no sistema de saúde.

AbstractDelays in treating breast cancer have been associated with a more advanced stage of the disease and a decrease in patient survival rates. The scope of this integrative review was to analyze the main causal factors and types of patient and system delays. The underlying causal factors of delays were compared among studies conducted in developing and developed countries. Of the 53 studies selected, 24 were carried out in developing countries and 29 in developed countries, respectively. Non-attribution of symptoms to cancer, fear of the disease and treatment and low educational level were the most frequent causes of patient delay. Less comprehensive health insurance coverage, older/younger age and false negative diagnosis tests were the three most common causal factors of system delay. The effects of factors such as age were not decisive per se and depended mainly on the social and cultural context. Some factors caused both patient delay and system delay. Studies conducted in developing countries identified more causal factors of patient delay and had a stronger focus on patient delay or the combination of both. Studies conducted in developed countries had a stronger focus on aspects of system delay during treatment and guidance of breast cancer patients in the health care system.

ResumoO atraso no tratamento de câncer de mama foi associado com o aumento do palco da doença e a diminuição da sobrevida do paciente. O objetivo desta revisão integrativa foi a analise dos principais fatores causais e dos tipos de atraso. Sendo estes comparados entre estudos de países em desenvolvimento e desenvolvidos. Dos 53 estudos selecionados, 24 eram de países em desenvolvimento e 29 de países desenvolvidos, respectivamente. A não atribuição dos sintomas ao câncer, o medo e a menor escolaridade foram as causas mais citadas do atraso de paciente ao tratamento. Seguro menos abrangente, idade e testes diagnósticos falsos negativos foram às causas mais comuns identificadas do atraso do sistema. O efeito de vários fatores como o fator idade, dependeu principalmente do contexto social e cultural. Alguns fatores causaram tanto atraso relacionado ao paciente quanto ao sistema. Os estudos dos países em desenvolvimento identificaram mais fatores causais do atraso relacionado ao paciente, focando mais forte neste referido fator ou na combinação com o de sistema. Enquanto estudos de países desenvolvidos enfocaram com maior frequência aspectos do atraso de sistema durante o tratamento e a orientação de pacientes no sistema de saúde.

AbstractDelays in treating breast cancer have been associated with a more advanced stage of the disease and a decrease in patient survival rates. The scope of this integrative review was to analyze the main causal factors and types of patient and system delays. The underlying causal factors of delays were compared among studies conducted in developing and developed countries. Of the 53 studies selected, 24 were carried out in developing countries and 29 in developed countries, respectively. Non-attribution of symptoms to cancer, fear of the disease and treatment and low educational level were the most frequent causes of patient delay. Less comprehensive health insurance coverage, older/younger age and false negative diagnosis tests were the three most common causal factors of system delay. The effects of factors such as age were not decisive per se and depended mainly on the social and cultural context. Some factors caused both patient delay and system delay. Studies conducted in developing countries identified more causal factors of patient delay and had a stronger focus on patient delay or the combination of both. Studies conducted in developed countries had a stronger focus on aspects of system delay during treatment and guidance of breast cancer patients in the health care system.

Apesar da inexatidão conceitual e de métodos de aferição, a OMS estima que cerca de 10% da população mundial apresente alguma forma de deficiência. Com a finalidade de investigar a prevalência e a etiologia das deficiências e verificar se elas estariam associadas à endogamia, foi realizado um estudo epidemiológico transversal com uso do método do informante envolvendo cinco municípios do Estado do Rio Grande do Norte, no Nordeste brasileiro; nos quais foram estimadas frequências de casamentos consanguíneos que variam de 9 a 32%. A prevalência média estimada para deficiências nos cinco municípios amostrados foi de 4,53%, obtida por meio de entrevistas envolvendo 37,87% de uma população de 39.054 habitantes. Em média, 25% dos casais consanguíneos e 12% dos não consanguíneos apresentaram um ou mais filhos com alguma deficiência. A elevada prevalência de pessoas com deficiência no Nordeste brasileiro pode ter associação com a manutenção da tradição de casamentos consanguíneos nessas populações e parte dessas deficiências pode ser causada por doenças genéticas.

Despite conceptual inaccuracies and methods of measurement, the WHO estimates that about 10% of the world population has some form of disability. In order to investigate the prevalence and etiology of disabilities and to evaluate if they could be associated with inbreeding, a cross-sectional epidemiological study was conducted using the informant method in five communities of the state Rio Grande do Norte in the Brazilian Northeast, in which consanguineous marriages frequencies varied between 9 and 32%. The average prevalence of disabilities in the five sampled communities was 4.53%, obtained by interviews that involved 37.87% of a population of 39,054 inhabitants. On average, 25% of consanguineous and 12% of non-consanguineous couples had one or more children with disabilities. The increased rate of individuals with disabilities in the Brazilian Northeast could be associated with the maintenance of the tradition of consanguineous marriages in these populations and some of these disabilities may be caused by genetic disorders.

Apesar da inexatidão conceitual e de métodos de aferição, a OMS estima que cerca de 10% da população mundial apresente alguma forma de deficiência. Com a finalidade de investigar a prevalência e a etiologia das deficiências e verificar se elas estariam associadas à endogamia, foi realizado um estudo epidemiológico transversal com uso do método do informante envolvendo cinco municípios do Estado do Rio Grande do Norte, no Nordeste brasileiro; nos quais foram estimadas frequências de casamentos consanguíneos que variam de 9 a 32%. A prevalência média estimada para deficiências nos cinco municípios amostrados foi de 4,53%, obtida por meio de entrevistas envolvendo 37,87% de uma população de 39.054 habitantes. Em média, 25% dos casais consanguíneos e 12% dos não consanguíneos apresentaram um ou mais filhos com alguma deficiência. A elevada prevalência de pessoas com deficiência no Nordeste brasileiro pode ter associação com a manutenção da tradição de casamentos consanguíneos nessas populações e parte dessas deficiências pode ser causada por doenças genéticas.

Despite conceptual inaccuracies and methods of measurement, the WHO estimates that about 10% of the world population has some form of disability. In order to investigate the prevalence and etiology of disabilities and to evaluate if they could be associated with inbreeding, a cross-sectional epidemiological study was conducted using the informant method in five communities of the state Rio Grande do Norte in the Brazilian Northeast, in which consanguineous marriages frequencies varied between 9 and 32%. The average prevalence of disabilities in the five sampled communities was 4.53%, obtained by interviews that involved 37.87% of a population of 39,054 inhabitants. On average, 25% of consanguineous and 12% of non-consanguineous couples had one or more children with disabilities. The increased rate of individuals with disabilities in the Brazilian Northeast could be associated with the maintenance of the tradition of consanguineous marriages in these populations and some of these disabilities may be caused by genetic disorders.

A new autosomal recessive genetic condition, the SPOAN syndrome (an acronym for spastic paraplegia, optic atrophy and neuropathy syndrome), was recently discovered in an isolated region of the State of Rio Grande do Norte in Northeast Brazil, in a population that was identified by the IBGE (Brazilian Institute of Geography and Statistics) as belonging to the Brazilian communities with the highest rates of "deficiencies" (Neri, 2003), a term used to describe diseases, malformations, and handicaps in general. This prompted us to conduct a study of consanguinity levels in five of its municipal districts by directly interviewing their inhabitants. Information on 7,639 couples (corresponding to about 40% of the whole population of the studied districts) was obtained. The research disclosed the existence of very high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting the presence of a direct association between genetic diseases such as the SPOAN syndrome, genetic drift and inbreeding levels. This fact calls for the introduction of educational programs for the local populations, as well as for further studies aiming to identify and characterize other genetic conditions. Epidemiological strategies developed to collect inbreeding data, with the collaboration of health systems available in the region, might be very successful in the prospecting of genetic disorders.

The D-type cyclins form complexes with the cyclin dependent (CD) kinases CDK4 and CDK6 and promote the G1-S phase transition of the cell cycle by antagonizing the retinoblastoma suppresser protein pRB. In the developing nervous system D-type cyclins show spatially and temporally dynamic patterns of expression. We demonstrated that cyclin D1 was transiently expressed in differentiating spinal cord ventral interneurons while cyclin D3 protein was expressed in differentiating motor neurons and dorsal interneurons. This expression of cyclin D3 in neurons of the mantle zone was extended to all regions of the spinal cord at E15.5. The results suggest that cyclin D1 and D3 have specific functions in differentiating neurons. Similarly, in the developing midbrain-hindbrain region the D-type cyclins were expressed in different subsets of cells. Our results argue in favor of different functions for D-type cyclins during proliferation and differentiation of neural progenitors.