Characteristics of Esophageal Cancer Cases in Tanzania.

PurposeAge-standardized incidence rates for esophageal cancer (EC) in East Africa have been reported as disproportionately high compared with the worldwide incidence of nine per 100,000 population. This study aimed to characterize EC cases seen at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania.MethodsDemographic, clinical, and treatment variables were abstracted from charts of patients who received care for a diagnosis of EC at one or both institutions between 2011 and 2013. Categorical data were summarized as frequency counts and percentages. Continuous data were presented as medians and ranges. To compare men and women, Pearson's χ2 and two-sample t tests were applied.ResultsSeven hundred thirty-eight unique cases of EC were identified, of whom 68% were men and the median age was 60 years (range, 19 to 95 years). Notably, 93 cases (13%) were ≤ 40 years old at diagnosis. Squamous cell carcinoma was the dominant histology, comprising 90% of cases with documented histopathology. However, 34% of cases with a diagnosis of EC were not pathologically confirmed. The stage was documented as locoregional in 4% of cases, locally advanced in 20% of cases, metastatic in 14% of cases, and unknown in 63% of cases. Of 430 patients who received treatment at Ocean Road Cancer Institute, 76% were treated with radiation, 44% were treated with chemotherapy, 3% underwent a cancer-related surgical procedure, and 10% of cases received no cancer-directed therapy. The median overall survival for all patients was 6.9 months (95% CI, 5.0 to 12.8), regardless of stage at presentation.ConclusionBetween 2011 and 2013, cases of EC represented a large clinical burden at both institutions

De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits:report of 25 new individuals and review of the literature

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Smoking and mortality after breast cancer diagnosis: the health and functioning in women study.

We examined the effect of smoking on long-term mortality from breast cancer and other causes among a cohort of women with breast cancer. A total of 975 women diagnosed with breast cancer and aged 40-84 years were followed for a median follow-up of 11 years in the U.S. Health and Functioning in Women (HFW) study. The impact of the individual smoking status and smoking intensity reported in the first few months following breast cancer diagnosis on the risk of mortality from breast cancer and other causes was examined using Cox proportional hazards models. In this study, former smoking was associated with increased risk of other-cause mortality (hazard ratio [HR] = 1.47, 95% confidence interval [CI]: 1.13-1.90), and the risk doubled with increased intensity (HR for <50 pack-years [py]: 1.36, 95% CI: 1.03-1.79; HR for ≥50 py: 2.45, 95% CI: 1.41-4.23). Current smoking (HR = 2.45, 95% CI: 1.81-3.32) and each additional 10 py smoked (HR = 1.16, 95% CI: 1.11-1.22) were associated with statistically significant increases in the risk of other-cause mortality. The effect of current smoking on other-cause mortality decreased with advancing stage and increasing body mass index (BMI). Breast cancer-specific mortality was associated with current smoking of ≥50 py (HR = 2.36, 95% CI: 1.26-4.44), and each additional 10 py smoked (HR = 1.07, 95% CI: 1.01-1. 14). Current smoking, but not former smoking, was associated with increased risk of breast cancer-specific mortality in women with local disease (HR = 2.32, 95% CI: 1.32-4.09), but not in those with regional and distant disease (HR = 1.10, 95% CI: 0.73-1.68). Our findings suggest that current smoking at the time of breast cancer diagnosis may be associated with increased risk of breast-cancer specific and other-cause mortality, whereas former smoking is associated with increased risk of other-cause mortality. Smoking cessation at the time of diagnosis may lead to better prognosis among women with breast cancer

The impact of functional limitations on long-term outcomes among African-American and white women with breast cancer: a cohort study

OBJECTIVES: We examined the impact of functional limitations and functional decline during the first year following breast cancer diagnosis on the risk of mortality from breast cancer and other causes among African-American and white women, respectively. DESIGN: The Health and Functioning in Women (HFW) cohort study. SETTING: Detroit, Michigan, USA. PARTICIPANTS: A total of 162 African-American and 813 white women aged 40–84 years with newly diagnosed breast cancer identified through the Metropolitan Detroit Cancer Surveillance System over a 7-month period between 1984 and 1985 and followed for up to 28 years (median 11 years). OUTCOME MEASURES: Risk of mortality from breast cancer and other causes. RESULTS: Statistically significant increases in the risk of other-cause mortality were found for each unit increase in the number of self-reported functional limitations (HR=1.08, 95% CI 1.03 to 1.14), 0 vs ≥1 functional limitations (HR=1.47, 95% CI 1.13 to 1.91), difficulty in pushing or pulling large objects (HR=1.34, 95% CI 1.04 to 1.73), writing or handling small objects (HR=1.56, 95% CI 1.00 to 2.44), and walking half a mile (HR=1.60, 95% CI 1.19 to 2.14). Functional limitations and functional decline did not explain racial disparities in the survival of this cohort. Functional decline was associated with increased risk of other-cause mortality in women with regional and remote disease but not in women with localised disease. Whereas measures of functional limitation were not associated with breast cancer-specific mortality, each unit of functional decline (HR=1.17, 95% CI 1.05 to 1.31) and decline in the ability to sit ≥1 h (HR=2.06, 95% CI 1.13 to 3.76) were associated with increased risk of breast cancer-specific mortality. Measures of functional decline were associated with increased risk of breast cancer mortality in overweight and obese women, but not in women of normal weight. CONCLUSIONS: Whereas functional limitations were associated with increased risk of other-cause mortality, functional decline was associated with increased risk of breast cancer mortality

The impact of functional limitations on long-term outcomes among African-American and white women with breast cancer: a cohort study.

ObjectivesWe examined the impact of functional limitations and functional decline during the first year following breast cancer diagnosis on the risk of mortality from breast cancer and other causes among African-American and white women, respectively.DesignThe Health and Functioning in Women (HFW) cohort study.SettingDetroit, Michigan, USA.ParticipantsA total of 162 African-American and 813 white women aged 40-84 years with newly diagnosed breast cancer identified through the Metropolitan Detroit Cancer Surveillance System over a 7-month period between 1984 and 1985 and followed for up to 28 years (median 11 years).Outcome measuresRisk of mortality from breast cancer and other causes.ResultsStatistically significant increases in the risk of other-cause mortality were found for each unit increase in the number of self-reported functional limitations (HR=1.08, 95% CI 1.03 to 1.14), 0 vs ≥1 functional limitations (HR=1.47, 95% CI 1.13 to 1.91), difficulty in pushing or pulling large objects (HR=1.34, 95% CI 1.04 to 1.73), writing or handling small objects (HR=1.56, 95% CI 1.00 to 2.44), and walking half a mile (HR=1.60, 95% CI 1.19 to 2.14). Functional limitations and functional decline did not explain racial disparities in the survival of this cohort. Functional decline was associated with increased risk of other-cause mortality in women with regional and remote disease but not in women with localised disease. Whereas measures of functional limitation were not associated with breast cancer-specific mortality, each unit of functional decline (HR=1.17, 95% CI 1.05 to 1.31) and decline in the ability to sit ≥1 h (HR=2.06, 95% CI 1.13 to 3.76) were associated with increased risk of breast cancer-specific mortality. Measures of functional decline were associated with increased risk of breast cancer mortality in overweight and obese women, but not in women of normal weight.ConclusionsWhereas functional limitations were associated with increased risk of other-cause mortality, functional decline was associated with increased risk of breast cancer mortality

The impact of functional limitations on long-term outcomes among African-American and white women with breast cancer: a cohort study.

ObjectivesWe examined the impact of functional limitations and functional decline during the first year following breast cancer diagnosis on the risk of mortality from breast cancer and other causes among African-American and white women, respectively.DesignThe Health and Functioning in Women (HFW) cohort study.SettingDetroit, Michigan, USA.ParticipantsA total of 162 African-American and 813 white women aged 40-84 years with newly diagnosed breast cancer identified through the Metropolitan Detroit Cancer Surveillance System over a 7-month period between 1984 and 1985 and followed for up to 28 years (median 11 years).Outcome measuresRisk of mortality from breast cancer and other causes.ResultsStatistically significant increases in the risk of other-cause mortality were found for each unit increase in the number of self-reported functional limitations (HR=1.08, 95% CI 1.03 to 1.14), 0 vs ≥1 functional limitations (HR=1.47, 95% CI 1.13 to 1.91), difficulty in pushing or pulling large objects (HR=1.34, 95% CI 1.04 to 1.73), writing or handling small objects (HR=1.56, 95% CI 1.00 to 2.44), and walking half a mile (HR=1.60, 95% CI 1.19 to 2.14). Functional limitations and functional decline did not explain racial disparities in the survival of this cohort. Functional decline was associated with increased risk of other-cause mortality in women with regional and remote disease but not in women with localised disease. Whereas measures of functional limitation were not associated with breast cancer-specific mortality, each unit of functional decline (HR=1.17, 95% CI 1.05 to 1.31) and decline in the ability to sit ≥1 h (HR=2.06, 95% CI 1.13 to 3.76) were associated with increased risk of breast cancer-specific mortality. Measures of functional decline were associated with increased risk of breast cancer mortality in overweight and obese women, but not in women of normal weight.ConclusionsWhereas functional limitations were associated with increased risk of other-cause mortality, functional decline was associated with increased risk of breast cancer mortality