An investigation of cancer survival inequalities associated with individual-level socio-economic status, area-level deprivation, and contextual effects, in a cancer patient cohort in England and Wales

Background People living in more deprived areas of high-income countries have lower cancer survival than those in less deprived areas. However, associations between individual-level socio-economic circumstances and cancer survival are relatively poorly understood. Moreover, few studies have addressed contextual effects, where associations between individual-level socio-economic status and cancer survival vary depending on area-based deprivation. Methods Using 9276 individual-level observations from a longitudinal study in England and Wales, we examined the association with cancer survival of area-level deprivation and individual-level occupation, education, and income, for colorectal, prostate and breast cancer patients aged 20–99 at diagnosis. With flexible parametric excess hazard models, we estimated excess mortality across individual-level and area-level socio-economic variables and investigated contextual effects. Results For colorectal cancers, we found evidence of an association between education and cancer survival in men with Excess Hazard Ratio (EHR) = 0.80, 95% Confidence Interval (CI) = 0.60;1.08 comparing “degree-level qualification and higher” to “no qualification” and EHR = 0.74 [0.56;0.97] comparing “apprenticeships and vocational qualification” to “no qualification”, adjusted on occupation and income; and between occupation and cancer survival for women with EHR = 0.77 [0.54;1.10] comparing “managerial/professional occupations” to “manual/technical,” and EHR = 0.81 [0.63;1.06] comparing “intermediate” to “manual/technical”, adjusted on education and income. For breast cancer in women, we found evidence of an association with income (EHR = 0.52 [0.29;0.95] for the highest income quintile compared to the lowest, adjusted on education and occupation), while for prostate cancer, all three individual-level socio-economic variables were associated to some extent with cancer survival. We found contextual effects of area-level deprivation on survival inequalities between occupation types for breast and prostate cancers, suggesting wider individual-level inequalities in more deprived areas compared to least deprived areas. Individual-level income inequalities for breast cancer were more evident than an area-level differential, suggesting that area-level deprivation might not be the most effective measure of inequality for this cancer. For colorectal cancer in both sexes, we found evidence suggesting area- and individual-level inequalities, but no evidence of contextual effects. Conclusions Findings highlight that both individual and contextual effects contribute to inequalities in cancer outcomes. These insights provide potential avenues for more effective policy and practice.

Socio-Economic Inequalities in Lung Cancer Outcomes: An Overview of Systematic Reviews

In the past decade, evidence has accumulated about socio-economic inequalities in very diverse lung cancer outcomes. To better understand the global effects of socio-economic factors in lung cancer, we conducted an overview of systematic reviews. Four databases were searched for systematic reviews reporting on the relationship between measures of socio-economic status (SES) (individual or area-based) and diverse lung cancer outcomes, including epidemiological indicators and diagnosis- and treatment-related variables. AMSTAR-2 was used to assess the quality of the selected systematic reviews. Eight systematic reviews based on 220 original studies and 8 different indicators were identified. Compared to people with a high SES, people with a lower SES appear to be more likely to develop and die from lung cancer. People with lower SES also have lower cancer survival, most likely due to the lower likelihood of receiving both traditional and next-generation treatments, higher rates of comorbidities, and the higher likelihood of being admitted as emergency. People with a lower SES are generally not diagnosed at later stages, but this may change after broader implementation of lung cancer screening, as early evidence suggests that there may be socio-economic inequalities in its use.

RNA binding protein HuD promotes autophagy and tumor stress survival by suppressing mTORC1 activity and augmenting ARL6IP1 levels

Background Neuronal-origin HuD (ELAVL4) is an RNA binding protein overexpressed in neuroblastoma (NB) and certain other cancers. The RNA targets of this RNA binding protein in neuroblastoma cells and their role in promoting cancer survival have been unexplored. In the study of modulators of mTORC1 activity under the conditions of optimal cell growth and starvation, the role of HuD and its two substrates were studied. Methods RNA immunoprecipitation/sequencing (RIP-SEQ) coupled with quantitative real-time PCR were used to identify substrates of HuD in NB cells. Validation of the two RNA targets of HuD was via reverse capture of HuD by synthetic RNA oligoes from cell lysates and binding of RNA to recombinant forms of HuD in the cell and outside of the cell. Further analysis was via RNA transcriptome analysis of HuD silencing in the test cells. Results In response to stress, HuD was found to dampen mTORC1 activity and allow the cell to upregulate its autophagy levels by suppressing mTORC1 activity. Among mRNA substrates regulated cell-wide by HuD, GRB-10 and ARL6IP1 were found to carry out critical functions for survival of the cells under stress. GRB-10 was involved in blocking mTORC1 activity by disrupting Raptor-mTOR kinase interaction. Reduced mTORC1 activity allowed lifting of autophagy levels in the cells required for increased survival. In addition, ARL6IP1, an apoptotic regulator in the ER membrane, was found to promote cell survival by negative regulation of apoptosis. As a therapeutic target, knockdown of HuD in two xenograft models of NB led to a block in tumor growth, confirming its importance for viability of the tumor cells. Cell-wide RNA messages of these two HuD substrates and HuD and mTORC1 marker of activity significantly correlated in NB patient populations and in mouse xenografts. Conclusions HuD is seen as a novel means of promoting stress survival in this cancer type by downregulating mTORC1 activity and negatively regulating apoptosis.

Population-based survival for cancer patients in Saudi Arabia for the years 2005–2009

The Saudi Cancer Registry reported in 2007 the 5-year observed survival for the most common cancer sites for the years 1994–2004. In this report we looked at the cancer survival in the period 2005–2009 and evaluated the trend over the 15 years period from 1994 to 2009. Cases of the top 14 cancer sites reported by the population based Saudi Cancer Registry from 1 January 2005 to December 31, 2009, were submitted for survival analysis. The vital status of those patients was collected. Analysis of survival for the above period was compared with the prior reported 2 periods (1994–1999, 2000–2004). In addition, analysis was done according to age, sex, disease stage and the province. Data of 25,969 patients of the commonest cancer sites were submitted. Of those 14,146 patients (54%) had complete demographic data available and vital status was reported. Thyroid cancer had the highest 5- year observed survival of 94% (95% confidence interval (CI) 93–95%)), followed by Breast (72%, 95% CI 71–74%). In hematological malignancies, Hodgkin’s Lymphoma had the highest 5-year survival of 86% (95% CI 84–88%). Survival rates has improved in most of the cancers sites for the studied periods except for lung, uterine and Hodgkin’s lymphoma which plateaued. Our study confirms a steady improvement in the 5-year observed survival over time for the majority of cancers. Our survival data were comparable to western countries. This data should be used by policy makers to improve on cancer care in the kingdom.

Non-parametric estimation of reference adjusted, standardised probabilities of all-cause death and death due to cancer for population group comparisons

Background Ensuring fair comparisons of cancer survival statistics across population groups requires careful consideration of differential competing mortality due to other causes, and adjusting for imbalances over groups in other prognostic covariates (e.g. age). This has typically been achieved using comparisons of age-standardised net survival, with age standardisation addressing covariate imbalance, and the net estimates removing differences in competing mortality from other causes. However, these estimates lack ease of interpretability. In this paper, we motivate an alternative non-parametric approach that uses a common rate of other cause mortality across groups to give reference-adjusted estimates of the all-cause and cause-specific crude probability of death in contrast to solely reporting net survival estimates. Methods We develop the methodology for a non-parametric equivalent of standardised and reference adjusted crude probabilities of death, building on the estimation of non-parametric crude probabilities of death. We illustrate the approach using regional comparisons of survival following a diagnosis of rectal cancer for men in England. We standardise to the covariate distribution and other cause mortality of England as a whole to offer comparability, but with close approximation to the observed all-cause region-specific mortality. Results The approach gives comparable estimates to observed crude probabilities of death, but allows direct comparison across population groups with different covariate profiles and competing mortality patterns. In our illustrative example, we show that regional variations in survival following a diagnosis of rectal cancer persist even after accounting for the variation in deprivation, age at diagnosis and other cause mortality. Conclusions The methodological approach of using standardised and reference adjusted metrics offers an appealing approach for future cancer survival comparison studies and routinely published cancer statistics. Our non-parametric estimation approach through the use of weighting offers the ability to estimate comparable survival estimates without the need for statistical modelling.

Gynecological Health Concerns in Women with Schizophrenia and Related Disorders: A Narrative Review of Recent Studies

Sex and age are important factors influencing physical and mental health in schizophrenia. Our goal was to review the recent literature for associations between gynecological conditions and psychotic illness and to propose integrated strategies for their management in order to improve overall health outcomes in women. We addressed the following questions: What are the prevalence and risk factors of gynecological disorders in women with schizophrenia or delusional disorder (DD)? What are the rates of uptake of gynecological cancer screening and mortality in this population? What role does menopause play? We found an increased incidence of breast cancer in women with schizophrenia. Other gynecological comorbidities were less frequent, but the field has been understudied. Low rates of breast and cervical cancer screening characterize women with schizophrenia. Menopause, because of endocrine changes, aging effects, and resultant comorbidity is associated with high rates of aggressive breast cancer in this population. Uterine and ovarian cancers have been less investigated. Psychosocial determinants of health play an important role in cancer survival. The findings lead to the recommendation that primary care, psychiatry, gynecology, oncology, and endocrinology collaborate in early case finding, in research into etiological links, and in improvement of prevention and treatment.