Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle.

Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere replication is altered at shortened telomeres. R-loop persistence at short telomeres contributes to activation of the DNA damage response (DDR) and promotes recruitment of the Rad51 recombinase. Thus, the telomere length-dependent regulation of TERRA and TERRA R-loops is a critical determinant of the rate of replicative senescence.

Adaptation to DNA damage checkpoint in senescent telomerase-negative cells promotes genome instability.

In cells lacking telomerase, telomeres gradually shorten during each cell division to reach a critically short length, permanently activate the DNA damage checkpoint, and trigger replicative senescence. The increase in genome instability that occurs as a consequence may contribute to the early steps of tumorigenesis. However, because of the low frequency of mutations and the heterogeneity of telomere-induced senescence, the timing and mechanisms of genome instability increase remain elusive. Here, to capture early mutation events during replicative senescence, we used a combined microfluidic-based approach and live-cell imaging in yeast. We analyzed DNA damage checkpoint activation in consecutive cell divisions of individual cell lineages in telomerase-negative yeast cells and observed that prolonged checkpoint arrests occurred frequently in telomerase-negative lineages. Cells relied on the adaptation to the DNA damage pathway to bypass the prolonged checkpoint arrests, allowing further cell divisions despite the presence of unrepaired DNA damage. We demonstrate that the adaptation pathway is a major contributor to the genome instability induced during replicative senescence. Therefore, adaptation plays a critical role in shaping the dynamics of genome instability during replicative senescence.

Elucidation of the DNA end-replication problem in Saccharomyces cerevisiae.

The model for telomere shortening at each replication cycle is currently incomplete, and the exact contribution of the telomeric 3' overhang to the shortening rate remains unclear. Here, we demonstrate key steps of the mechanism of telomere replication in Saccharomyces cerevisiae. By following the dynamics of telomeres during replication at near-nucleotide resolution, we find that the leading-strand synthesis generates blunt-end intermediates before being 5'-resected and filled in. Importantly, the shortening rate is set by positioning the last Okazaki fragments at the very ends of the chromosome. Thus, telomeres shorten in direct proportion to the 3' overhang lengths of 5-10 nucleotides that are present in parental templates. Furthermore, the telomeric protein Cdc13 coordinates leading- and lagging-strand syntheses. Taken together, our data unravel a precise choreography of telomere replication elucidating the DNA end-replication problem and provide a framework to understand the control of the cell proliferation potential.

Inequalities in the burden of female breast cancer in Brazil, 1990-2017.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer in women and the leading cause of cancer death among females worldwide. In recent decades, breast cancer death rates have been stable or decreasing in more developed regions; however, this has not been observed in less developed regions. This study aims to evaluate inequalities in the burden of female breast cancer in Brazil including an analysis of interregional and interstate patterns in incidence, mortality and disability-adjusted life years (DALYs) rates from 1990 to 2017, and mortality-to-incidence ratio (MIR), and their association with the Socio-demographic Index (SDI). METHODS: Using estimates from the global burden of disease (GBD) study, we applied a spatial exploratory analysis technique to obtain measurements of global and local spatial correlation. Percentage changes of breast cancer incidence, mortality, and DALYs rates between 1990 and 2017 were calculated, and maps were developed to show the spatial distribution of the variables. Spatial panel models were adjusted to investigate the association between rates and SDI in Brazilian states. RESULTS: In Brazil, while breast cancer mortality rate have had modest reduction (-4.45%; 95% UI: -6.97; -1.76) between 1990 and 2017, the incidence rate increased substantially (+39.99%; 95% UI: 34.90; 45.39). Breast cancer incidence and mortality rates in 1990 and 2017 were higher in regions with higher SDI, i.e., the most developed ones. While SDI increased in all Brazilian states between 1990 and 2017, notably in less developed regions, MIR decreased, more notably in more developed regions. The SDI had a positive association with incidence rate and a negative association with MIR. CONCLUSION: Such findings suggest an improvement in breast cancer survival in the period, which may be related to a broader access to diagnostic methods and treatment. This study also revealed the inequality in breast cancer outcomes among Brazilian states and may guide public policy priorities for disease control in the country.

The many types of heterogeneity in replicative senescence.

Replicative senescence, which is induced by telomere shortening, underlies the loss of regeneration capacity of organs and is ultimately detrimental to the organism. At the same time, it is required to protect organisms from unlimited cell proliferation that may arise from numerous stimuli or deregulations. One important feature of replicative senescence is its high level of heterogeneity and asynchrony, which promote genome instability and senescence escape. Characterizing this heterogeneity and investigating its sources are thus critical to understanding the robustness of replicative senescence. Here we review the different aspects of senescence driven by telomere attrition that are subject to variation in Saccharomyces cerevisiae, the current understanding of the molecular processes at play, and the consequences of heterogeneity in replicative senescence.

[Breast cancer mortality in Brazilian municipalities and associated factorsMortalidad por cáncer de mama en municipios brasileños y factores asociados]. / Comportamento da mortalidade por câncer de mama nos municípios brasileiros e fatores associados.

OBJECTIVE: To analyze breast cancer mortality trends in Brazilian municipalities and assess the influence of socioeconomic and demographic factors on mortality rates. METHODS: Age-adjusted mortality rates were calculated for the periods centered in 1990, 2000, and 2010 and corrected for ill-defined causes of death. After that, panel data regression models were developed for analysis of the association between the factors of interest and the mortality rate from breast cancer in Brazilian municipalities. RESULTS: A growing trend was detected in breast cancer mortality in Brazil. However, the models showed that the mortality could have decreased (negative trend), especially in the Southeast and South regions, if some associated factors (such as income, education, longevity, fertility rate, health spending, and infrastructure, among others) had remained constant during the study period. Breast cancer mortality was positively/significantly associated with longevity and negatively/significantly associated with public health spending. Mortality was higher in the South and Southeast, in municipalities with more than 500 000 inhabitants and in those with population below 5 000. CONCLUSIONS: The growth in per capita income, the increase in life expectancy, and the decrease in fertility rates may be associated with high breast cancer mortality and a trend towards increased mortality from this cancer in Brazilian municipalities.

OBJETIVO: Analizar las tendencias de la mortalidad por cáncer de mama en municipios brasileños y evaluar la influencia de factores socioeconómicos y demográficos sobre las tasas de mortalidad. MÉTODOS: Se calcularon las tasas de mortalidad, ajustadas por grupo etario y corregidas por causas mal definidas, para los años 1990, 2000 y 2010. Posteriormente, se calcularon modelos de regresión, a partir de datos de panel, que permitieron verificar el grado de asociación entre distintos factores de interés y la tasa de mortalidad por esta enfermedad. RESULTADOS: Se verificó que había una tendencia al aumento de la mortalidad en el país. Sin embargo, los modelos indicaron que la mortalidad podría haber disminuido (tendencia negativa), principalmente en el sudeste y el sur, si algunos factores asociados (por ejemplo, nivel de ingresos, educación, longevidad, tasa de fecundidad, gastos en salud, infraestructura, entre otros) hubieran permanecido constantes durante el período en estudio. Se observó que la mortalidad por cáncer de mama presentó una asociación positiva y significativa con la longevidad, y negativa y significativa con el nivel del gasto público en salud. La mortalidad fue mayor en las zonas sur y sudeste, en los municipios con más de 500 000 habitantes y en aquellos cuya población es inferior a 5000. CONCLUSIONES: El aumento de los ingresos per cápita, el incremento de la esperanza de vida y la disminución de la tasa de fecundidad pueden estar asociados a tasas altas de mortalidad por cáncer de mama y a una tendencia al aumento de dicha mortalidad en los municipios brasileños.

Length-dependent processing of telomeres in the absence of telomerase.

In the absence of telomerase, telomeres progressively shorten with every round of DNA replication, leading to replicative senescence. In telomerase-deficient Saccharomyces cerevisiae, the shortest telomere triggers the onset of senescence by activating the DNA damage checkpoint and recruiting homologous recombination (HR) factors. Yet, the molecular structures that trigger this checkpoint and the mechanisms of repair have remained elusive. By tracking individual telomeres, we show that telomeres are subjected to different pathways depending on their length. We first demonstrate a progressive accumulation of subtelomeric single-stranded DNA (ssDNA) through 5'-3' resection as telomeres shorten. Thus, exposure of subtelomeric ssDNA could be the signal for cell cycle arrest in senescence. Strikingly, early after loss of telomerase, HR counteracts subtelomeric ssDNA accumulation rather than elongates telomeres. We then asked whether replication repair pathways contribute to this mechanism. We uncovered that Rad5, a DNA helicase/Ubiquitin ligase of the error-free branch of the DNA damage tolerance (DDT) pathway, associates with native telomeres and cooperates with HR in senescent cells. We propose that DDT acts in a length-independent manner, whereas an HR-based repair using the sister chromatid as a template buffers precocious 5'-3' resection at the shortest telomeres.

Hog1 acts in a Mec1-independent manner to counteract oxidative stress following telomerase inactivation in Saccharomyces cerevisiae.

Replicative senescence is triggered when telomeres reach critically short length and activate permanent DNA damage checkpoint-dependent cell cycle arrest. Mitochondrial dysfunction and increase in oxidative stress are both features of replicative senescence in mammalian cells. However, how reactive oxygen species levels are controlled during senescence is elusive. Here, we show that reactive oxygen species levels increase in the telomerase-negative cells of Saccharomyces cerevisiae during replicative senescence, and that this coincides with the activation of Hog1, a mammalian p38 MAPK ortholog. Hog1 counteracts increased ROS levels during replicative senescence. While Hog1 deletion accelerates replicative senescence, we found this could stem from a reduced cell viability prior to telomerase inactivation. ROS levels also increase upon telomerase inactivation when Mec1, the yeast ortholog of ATR, is mutated, suggesting that oxidative stress is not simply a consequence of DNA damage checkpoint activation in budding yeast. We speculate that oxidative stress is a conserved hallmark of telomerase-negative eukaryote cells, and that its sources and consequences can be dissected in S. cerevisiae.

[Survival rate of laryngeal cancer patients treated in Brazil's Unified Health System - SUS, 2002-2010]. / Sobrevida por câncer de laringe em pacientes tratados no Sistema Único de Saúde - SUS, 2002-2010.

The scope of this article was to analyze the five-year survival rate among patients with laryngeal cancer treated in the Unified Health System in Brazil and its regions between January 2002 and June 2010. There is still scarce information in Brazil regarding the scale and survival rate of laryngeal cancer patients, which makes it difficult to adopt specific strategies for the control of the condition in the country. A retrospective cohort study based on the National Oncology Database was conducted, and the survival probability rate for laryngeal cancer according to age, sex and Brazilian regions/states was estimated using the Kaplan-Meier method. The log-rank test was used to assess the differences observed, considering a 5% significance level. Survival in Brazil was estimated at 50.8% (95%CI: 49.9%-51.8%), being lower among male patients (49.1%; 95%CI: 48.10%-50.16%); between 50 and 60 years of age (48.4%; 95%CI: 46.7%-50.0%); for residents of the Northern region (45.5%; 95%CI: 39.5%-51.3%). The regional variation in the survival rate for laryngeal cancer in Brazil reveals disparities between Brazilian regions/states that may be linked to inequality of access to diagnosis and/or treatment.

O objetivo do artigo foi analisar a sobrevida de cinco anos em pacientes com câncer de laringe tratados no Sistema Único de Saúde no Brasil e regiões entre janeiro de 2002 e junho de 2010. São escassas as informações relativas à magnitude e sobrevida do câncer de laringe no país, o que dificulta a adoção de estratégias específicas para seu controle. Foi realizado um estudo de coorte retrospectiva a partir da Base Nacional em Oncologia. Estimou-se a probabilidade de sobrevida para o câncer de laringe segundo faixa etária, sexo e regiões/estados brasileiros por meio do método de Kaplan-Meier. O teste de log-rank foi aplicado para avaliar as diferenças na sobrevida, considerando-se o nível de significância de 5%. A sobrevida no Brasil foi estimada em 50,8% (IC95%: 49,9-51,8), sendo menor em pacientes do sexo masculino (49,1%; IC95%: 48,10-50,16); com idade entre 50 e 60 anos (48,4%; IC95%: 46,7-50,0); e para moradores da região Norte (45,5%; IC95%: 39,5-51,3). A variação na sobrevida para o câncer de laringe em relação aos estados e às regiões do país aponta disparidades que podem estar relacionadas à desigualdade de acesso ao diagnóstico e/ou tratamento.

Quality of life of women who underwent breast cancer treatment relative to sociodemographic, behavioral, and clinical factors.

OBJECTIVE: Patients with cancer often undergo multiple extended treatments that decrease their quality of life. However, the quality of life of women with breast cancer after they undergo treatment remains underexplored in Brazil. Therefore, this study determined sociodemographic, behavioral, and clinical factors related to the post-treatment quality of life of women with breast cancer. METHODS: This cross-sectional study involved 101 women diagnosed with breast cancer between 2014 and 2016 and treated at a Brazilian Oncology Reference Service. Data were collected from them using face-to-face surveys. Quality of life was evaluated using the European Organization for the Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) and EORTC Breast Cancer-specific Quality of Life questionnaire (EORTC QLQ-BR23). The data collected were analyzed using Student's t-test and Mann-Whitney U test. RESULTS: The median score on the global health, functional, and symptom scales of the EORTC QLQ-C30 was 75.00 (Interquartile range=33.33), 75.99 (Standard deviation [SD]=19.26), and 19.67 (SD=16.91), respectively. The mean score on the functional and symptom scales of the EORTC QLQ-BR23 was 61.89 (SD=17.21) and 20.12 (SD=16.94), respectively. Furthermore, higher post-treatment quality of life was found to be associated with being aged 50 or more, being Black, having eight or more years of education, having a partner, having a paying job, receiving treatment from the private healthcare system, having a higher income, living in the municipality where healthcare services are availed, engaging in physical activity, not smoking, being more religious, having more social support, not being overweight, having no comorbidities, and undergoing lumpectomy. CONCLUSION: Sociodemographic, behavioral, and clinical factors significantly impact the quality of life of women who undergo breast cancer treatment. Implementing interventions that improve health and reducing inequalities in the access to healthcare services can improve the quality of life of these patients. BACKGROUND: Sociodemographic, clinical, and lifestyle factors impact the quality of life of breast cancer survivors. BACKGROUND: Breast cancer therapy may affect future perspectives and emotional, cognitive, and sexual function. BACKGROUND: Some aspects of quality of life still require attention from health professionals. BACKGROUND: Higher post-treatment quality of life of women with breast cancer is linked to being aged 50 or more, being Black, having 8 or more years of education, having a partner, having a paying job, receiving care from private healthcare, having a high per capita income, residing in the municipality where the service is availed, engaging in physical activity, not smoking, greater religiosity, having more social support, having a normal weight, having no comorbidities, and undergoing lumpectomy.

Comparison of four different human papillomavirus genotyping methods in cervical samples: Addressing method-specific advantages and limitations.

Since human papillomavirus (HPV) is recognized as the causative agent of cervical cancer and associated with anogenital non-cervical and oropharyngeal cancers, the characterization of the HPV types circulating in different geographic regions is an important tool in screening and prevention. In this context, this study compared four methodologies for HPV detection and genotyping: real-time PCR (Cobas® HPV test), nested PCR followed by conventional Sanger sequencing, reverse hybridization (High + Low PapillomaStrip® kit) and next-generation sequencing (NGS) at an Illumina HiSeq2500 platform. Cervical samples from patients followed at the Family Health Strategy from Juiz de Fora, Minas Gerais, Brazil, were collected and subjected to the real-time PCR. Of those, 114 were included in this study according to the results obtained with the real-time PCR, considered herein as the gold standard method. For the 110 samples tested by at least one methodology in addition to real-time PCR, NGS showed the lowest concordance rates of HPV and high-risk HPV identification compared to the other three methods (67-75 %). Real-time PCR and Sanger sequencing showed the highest rates of concordance (97-100 %). All methods differed in their sensitivity and specificity. HPV genotyping contributes to individual risk stratification, therapeutic decisions, epidemiological studies and vaccine development, supporting approaches in prevention, healthcare and management of HPV infection.

TERRA and Telomere Maintenance in the Yeast Saccharomyces cerevisiae.

Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered. One of them, TERRA (TElomeric Repeat-containing RNA), starts in the subtelomeric regions towards the chromosome ends from different telomeres and has been extensively studied in many evolutionarily distant eukaryotes. Changes in TERRA's expression can lead to telomeric dysfunction, interfere with the replicative machinery and impact telomere length. TERRA also co-localizes in vivo with telomerase, and can form RNA:DNA hybrid structures called R-loops, which have been implicated in the onset of senescence and the alternative lengthening of telomere (ALT) pathway. Yet, the molecular mechanisms involving TERRA, as well as its function, remain elusive. Here, we review the current knowledge of TERRA transcription, structure, expression, regulation and its multiple telomeric and extra-telomeric functions in the budding yeast Saccharomyces cerevisiae.

The Polo kinase Cdc5 is regulated at multiple levels in the adaptation response to telomere dysfunction.

Telomere dysfunction activates the DNA damage checkpoint to induce a cell cycle arrest. After an extended period of time, however, cells can bypass the arrest and undergo cell division despite the persistence of the initial damage, a process called adaptation to DNA damage. The Polo kinase Cdc5 in Saccharomyces cerevisiae is essential for adaptation and for many other cell cycle processes. How the regulation of Cdc5 in response to telomere dysfunction relates to adaptation is not clear. Here, we report that Cdc5 protein level decreases after telomere dysfunction in a Mec1-, Rad53- and Ndd1-dependent manner. This regulation of Cdc5 is important to maintain long-term cell cycle arrest but not for the initial checkpoint arrest. We find that both Cdc5 and the adaptation-deficient mutant protein Cdc5-ad are heavily phosphorylated and several phosphorylation sites modulate adaptation efficiency. The PP2A phosphatases are involved in Cdc5-ad phosphorylation status and contribute to adaptation mechanisms. We finally propose that Cdc5 orchestrates multiple cell cycle pathways to promote adaptation.

Age-Period-Cohort Study of Breast Cancer Mortality in Brazil in State Capitals and in Non-Capital Municipalities from 1980 to 2019.

Breast cancer was identified as the cancer with the highest mortality rate among women in Brazil. This study analyzed the effects of age, period and birth cohort on the breast cancer mortality rate for Brazilian women, comparing state capitals and non-capital municipalities. Population and deaths data were extracted from the Brazilian Unified Health System database for women aged 30 years or older, for the years between 1980 and 2019. The effects were analyzed using the age-period-cohort model. Age effect on breast cancer mortality is observed in the model through higher mortality rates at older ages. Period effect is similar in all regions in the form of a marked increase in the rate ratio (RR) in non-capital municipalities by period than in state capitals. The RR of birth cohorts in the state capitals remained stable (north, northeast and central-west regions) or decreased followed by an increase in the most recent cohorts (Brazil as a whole and the southeast and south regions). The RR for the other municipalities, however, showed a progressive increase in the cohorts for all regions. Policies and actions focused on breast cancer in women should consider these differences among Brazilian regions, state capitals and other municipalities.

Frequency and factors associated with delay in breast cancer treatment in Brazil, according to data from the Oncology Panel, 2019-2020.

OBJECTIVE: to analyze treatment delay and the flow of care for women with breast cancer in Brazil in 2019 and 2020. METHOD: this was a follow-up study of breast cancer cases available from the Oncology Panel; a chi-square test and multilevel logistic regression were performed in order to analyze the explanatory variables associated with delay (greater than 60 days) in starting treatment. RESULTS: 22,956 cases (54.5%) with delay in treatment were identified in 2019 and 17,722 (48.7%) in 2020; the Southeast region (54.6%) had the greatest proportion of delay; delay was greater when treatment was provided outside the municipality of residence and lower in 2020 compared to 2019; most outward flows were to the capital cities in the same Federative Units of residence. CONCLUSION: strategies to reduce cancer treatment delay and optimize health care networks in the Federative Units should be prioritized.

Breast cancer survival and the health system in Brazil: an analysis of public and private healthcare.

Background: The incidence of breast cancer is increasing globally; however, survival outcomes vary and are lower in developing countries. Methods: We analyzed the 5- and 10-year survival rates for breast cancer according to the type of healthcare insurance (public vs. private) in a referral center for cancer care in the Brazilian southeast region. This hospital-based cohort study included 517 women diagnosed with invasive breast cancer between 2003 and 2005. The Kaplan-Meier method was used to estimate the probability of survival, and the Cox proportional hazards regression model was used to assess prognostic factors. Results: The 5- and 10-year breast cancer survival rates were as follows: private healthcare service survival rate of 80.6% (95% CI 75.0-85.0) and 71.5% (95% CI 65.4-77.1), respectively, and public healthcare service survival rate of 68.5% (95% CI 62.5-73.8) and 58.5% (95% CI 52.1-64.4), respectively. The main factors associated with the worst prognosis were lymph node involvement in both healthcare services and tumor size >2 cm only in public health services. The use of hormone therapy (private) and radiotherapy (public) was associated with the best survival rates. Conclusions: The survival discrepancies found between health services can be explained mainly by the difference in the stage of the disease at the time of diagnosis, indicating inequalities in access to the early detection of breast cancer.

COVID-19's intra-urban inequalities and social vulnerability in a medium-sized city.

BACKGROUND: Social conditions are related to the impact of epidemics on human populations. This study aimed to investigate the spatial distribution of cases, hospitalizations, and deaths from COVID-19 and its association with social vulnerability. METHODS: An ecological study was conducted in 81 urban regions (UR) of Juiz de Fora from March to November 2020. Exposure was measured using the Health Vulnerability Index (HVI), a synthetic indicator that combines socioeconomic and environmental variables from the Demographic Census 2010. Regression models were estimated for counting data with overdispersion (negative binomial generalized linear model) using Bayesian methods, with observed frequencies as the outcome, expected frequencies as the offset variable, and HVI as the explanatory variable. Unstructured random-effects (to capture the effect of unmeasured factors) and spatially structured effects (to capture the spatial correlation between observations) were included in the models. The models were estimated for the entire period and quarter. RESULTS: There were 30,071 suspected cases, 8,063 confirmed cases, 1,186 hospitalizations, and 376 COVID-19 deaths. In the second quarter of the epidemic, compared to the low vulnerability URs, the high vulnerability URs had a lower risk of confirmed cases (RR=0.61; CI95% 0.49-0.76) and a higher risk of hospitalizations (RR=1.65; CI95% 1.23-2.22) and deaths (RR=1.73; CI95% 1.08-2.75). CONCLUSIONS: The lower risk of confirmed cases in the most vulnerable UR probably reflected lower access to confirmatory tests, while the higher risk of hospitalizations and deaths must have been related to the greater severity of the epidemic in the city's poorest regions.

Temporal trends in social security benefits for female breast cancer in Brazil. / Tendência temporal dos benefícios previdenciários concedidos por câncer de mama feminino no Brasil.

The aim of this study was to assess temporal trends in disability benefits for breast cancer awarded to women by Brazil's National Social Security Institute. We conducted a time-series analysis of disability benefit incidence rates between 2007 and 2018 using joinpoint regression and data from the Unified Benefits Information System (SUIBE) and open access social security system database. The age-adjusted incidence rate increased by 6.7% per year between 2015 and 2018 after a period of stability between 2007 and 2014. The number of benefits granted to women aged 20-49 increased, on average, by 3.4% per year, showing a marked rise from 2015 to 2018 (10.4% per year). The findings highlight that breast cancer is an important cause of sick leave among female workers and that the incidence of the disease is growing in younger economically active women, reinforcing the importance of early referral to the Social Security Professional Rehabilitation Program to help workers return to work and readapt to working life.

O objetivo deste estudo foi avaliar a tendência temporal dos benefícios previdenciários concedidos pelo Instituto Nacional do Seguro Social a mulheres por câncer de mama. Foi realizado um estudo de tendência temporal das taxas de incidência dos auxílios por incapacidade temporária de espécie previdenciária concedidos por câncer de mama em mulheres entre 2007 e 2018 no Brasil, utilizando o Sistema Único de Informações de Benefícios e a base de dados abertos da Previdência Social. As análises de tendência foram realizadas através de regressão segmentada joinpoint. As taxas de incidência dos benefícios ajustadas por idade apresentaram estabilidade entre 2007 e 2015, seguida de elevação anual de 6,7% de 2015 a 2018. Houve aumento anual médio de 3,4% do número de benefícios concedidos a mulheres entre 20 e 49 anos, sendo mais evidente entre 2015 e 2018, com elevação de 10,4% ao ano. Este estudo demonstrou a importância do câncer de mama como causa de afastamento do trabalho em mulheres, com acometimento crescente das faixas etárias mais jovens e economicamente ativas, o que reforça a necessidade de abordagem precoce do Programa de Reabilitação Profissional da Previdência Social para a readaptação destas trabalhadoras em suas atividades ou a reinserção no mercado de trabalho.

The increasing burden of pancreatic cancer in Brazil from 2000 to 2019: estimates from the Global Burden of Disease Study 2019.

INTRODUCTION: Pancreatic cancer is increasing worldwide. The burden of pancreatic cancer in Brazil and its states was analyzed and compared with that from the USA and China. METHODS: This is a descriptive study of the incidence and mortality estimates from the Global Burden of Disease 2019 study, from 2000 to 2019. The Brazilian states presenting the highest and lowest socio-demographic index (SDI) were selected from each of the five regions. The SDI consists of the per capita income, education, and fertility rate of each population. RESULTS: A significant increase was found in age-standardized incidence and mortality of pancreatic cancer in all three countries, with differences in magnitude and annual increases. In Brazil, this incidence rose from 5.33 [95% Uncertainty Interval (UI): 5.06- 5.51] to 6.16 (95% UI: 5.68- 6.53) per 100,000 inhabitants. China and the Brazilian states with the lowest SDI, such as Pará and Maranhão, showed lower incidence and mortality rates, although presenting the highest annual increases. No difference was found between the sexes. A higher mortality rate was observed for those individuals of 70+ years, which was three to four times higher than those aged 50 to 69 years. CONCLUSIONS: The increasing burden of pancreatic cancer in the studied countries, and the higher estimates for the elderly in a fast-aging country such as Brazil, indicates that more resources and health policies will be necessary. The greatest increase in the states with lower SDI reflects inequalities in the access to diagnosis and registries of this cancer.