The contribution of prognostic factors to socio-demographic inequalities in breast cancer survival in Victoria, Australia.

BACKGROUND: Breast cancer survival in Australia varies according to socio-economic status (SES) and between rural and urban places of residence. Part of this disparity may be due to differences in prognostic factors at the time of diagnosis. METHODS: Women with invasive breast cancer diagnosed from 2008 until 2012 (n = 14,165) were identified from the Victorian Cancer Registry and followed up for 5 years, with death from breast cancer or other causes recorded. A prognostic score, based on stage at diagnosis, cancer grade, whether the cancer was detected via screening, reported comorbidities and age at diagnosis, was constructed for use in a mediation analysis. RESULTS: Five-year breast cancer mortality for women with breast cancer who were in the lowest quintile of SES (10.3%) was almost double that of those in the highest quintile (5.7%). There was a small survival advantage (1.7% on average, within each socio-economic quintile) of living in inner-regional areas compared with major cities. About half of the socio-economic disparity was mediated by prognostic factors, particularly stage at diagnosis and the presence of comorbidities. The inner-regional survival advantage was not due to differences in prognostic factors. CONCLUSIONS: Part of the socio-economic disparity in breast cancer survival could be addressed by earlier detection in, and improved general health for, more disadvantaged women. Further research is required to identify additional causes of socio-economic disparities as well as the observed inner-regional survival advantage.

Socio-economic and ethnocultural influences on geographical disparities in breast cancer screening participation in Victoria, Australia.

Objective: To examine the socio-economic and ethnocultural characteristics of geographical areas that may influence variation in breast cancer screening participation. Methods: In a cross-sectional analysis breast cancer screening participation for statistical areas in Victoria, Australia (2015-2017) was linked with data from the 2016 Australian Census. We selected four commonly used area-level measures of socio-economic status from the Australian Census (i) income (ii) educational level (iii) occupational status and (iv) employment profile. To assess the ethnocultural characteristics of statistical areas we used the Census measures (i) country of birth (ii) language spoken at home (iii) fluency in English (iv) religion and (v) the proportion of immigrants in an area, together with their recency of migration. Results: All the selected measures were related to screening participation. There was a high degree of association both within and between socio-economic and ethnocultural characteristics of areas as they relate to screening. Ethnocultural characteristics alone accounted for most of the explained geographical disparity in screening participation. Conclusions: Geographical disparities in breast cancer screening participation may be due to ethnocultural factors that are confounded with socio-economic factors.

Underutilisation of breast cancer prevention medication in Australia.

Increased implementation of proven prevention strategies is required to combat rising breast cancer incidence. We assessed use of risk reducing medication (RRMed) by Australian women at elevated breast cancer risk. Only 2.4% had ever used RRMed. Higher breast cancer risk was statistically significantly associated with use of RRMed (OR 1.82, 95%CI: 1.08-3.07, p = 0.02 for ≥30% lifetime risk compared with 16%-29% lifetime risk), but parity, education level and family history of breast cancer were not. Breast cancer prevention medications are underutilised. Efforts are needed to incorporate breast cancer risk assessment and risk management discussions into routine health assessments for women.

DNA Methylation in Peripheral Blood and Risk of Gastric Cancer: A Prospective Nested Case-control Study.

DNA methylation in peripheral blood is a potential biomarker of gastric cancer risk which could be used for early detection. We conducted a prospective case-control study nested within the Melbourne Collaborative Cohort Study. Genomic DNA was prepared from blood samples collected a median of 12 years before diagnosis for cases (N = 168). Controls (N = 163) were matched to cases on sex, year of birth, country of birth, and blood sample type using incidence density sampling. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450K Beadchip. Global measures of DNA methylation were defined as the median methylation M value, calculated for each of 13 CpG subsets representing genomic function, mean methylation and location, and reliability of measurement. Conditional logistic regression was conducted to assess associations between these global measures of methylation and gastric cancer risk, adjusting for Helicobacter pylori and other potential confounders. We tested nonlinear associations using quintiles of the global measure distribution. A genome-wide association study of DNA methylation and gastric cancer risk was also conducted (N = 484,989 CpGs) using conditional logistic regression, adjusting for potential confounders. Differentially methylated regions (DMR) were investigated using the R package DMRcate We found no evidence of associations with gastric cancer risk for individual CpGs or DMRs (P > 7.6 × 10-6). No evidence of association was observed with global measures of methylation (OR 1.07 per SD of overall median methylation; 95% confidence interval, 0.80-1.44; P = 0.65). We found no evidence that blood DNA methylation is prospectively associated with gastric cancer risk.Prevention Relevance: We studied DNA methylation in blood to try and predict who was at risk of gastric cancer before symptoms developed, by which stage survival is poor. We did not find any such markers, but the importance of early diagnosis in gastric cancer remains, and the search for markers continues.

Examining Health-Related Effects of Refurbishment to Parks in a Lower Socioeconomic Area: The ShadePlus Natural Experiment.

Degraded parks in disadvantaged areas are underutilized for recreation, which may impact long-term health. Using a natural experiment, we examined the effects of local government refurbishments to parks (n = 3 intervention; n = 3 comparison) in low socioeconomic areas (LSEA) of Melbourne on park use, health behavior, social engagement and psychological well-being. Amenities promoting physical activity and sun protection included walking paths, playground equipment and built shade. Outcomes were measured via systematic observations, and self-report surveys of park visitors over three years. The refurbishments significantly increased park use, while shade use increased only in parks with shade sails. A trend for increased social engagement was also detected. Findings infer improvement of quality, number and type of amenities in degraded parks can substantially increase park use in LSEA. Findings support provision of shade over well-designed playgrounds in future park refurbishments to enhance engagement and sun protection behavior. Further research should identify park amenities to increase physical activity.

Differences in cancer survival by remoteness of residence: an analysis of data from a population-based cancer registry.

PURPOSE: Cancer survival is generally lower for rural compared with urban residents, but findings have been inconsistent. We aimed to assess inequalities in cancer survival by remoteness of residence in Victoria, Australia. METHODS: Incident cancer cases diagnosed in 2001-2015 with 30 cancer types (n = 331,302) were identified through the Victorian Cancer Registry and followed to the end of 2015 through death registries. Five-year net survival was estimated using the Pohar-Perme method and differences assessed by excess mortality rate ratios (EMRRs) using Poisson regression, adjusting for sex, age and year of diagnosis. EMRRs adjusted for socio-economic disadvantage were also estimated. RESULTS: People living outside major cities had lower survival for 11 cancers: esophagus, stomach, colorectum, liver, gallbladder/biliary tract, pancreas, lung, connective/soft tissue, ovary, prostate, kidney. No differences in survival were found for cancers of uterus, small intestine and mesothelioma. After adjusting for socio-economic disadvantage, the observed differences in survival decreased for most cancers and disappeared for colorectal cancer, but they remained largely unchanged for cancers of esophagus, stomach, liver, pancreas, lung, connective/soft tissue, ovary and kidney. CONCLUSION: People with cancer residing outside major cities had lower survival from some cancers, which is partly due to the greater socio-economic disadvantage of rural residents.

Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis.

Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992-1999 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up = 15.7; range = 0.8-21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (p < 0.001), similar if they survived to 5 years (p = 0.4), and lower if they survived to 10 years (p = 0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR) per 10 nodes = 2.52 [95% CI:2.11-3.01]) and tumor grade (HR per grade = 1.62 [95% CI:1.34-1.96]). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis.

Dietary intake of one-carbon metabolism nutrients and DNA methylation in peripheral blood.

Background: Folate and other one-carbon metabolism nutrients are essential to enable DNA methylation to occur, but the extent to which their dietary intake influences methylation in adulthood is unclear. Objective: We assessed associations between dietary intake of these nutrients and DNA methylation in peripheral blood, overall and at specific genomic locations. Design: We conducted a cross-sectional study using baseline data and samples from 5186 adult participants in the Melbourne Collaborative Cohort Study (MCCS). Nutrient intake was estimated from a food-frequency questionnaire. DNA methylation was measured by using the Illumina Infinium HumanMethylation450 BeadChip array (HM450K). We assessed associations of intakes of folate, riboflavin, vitamins B-6 and B-12, methionine, choline, and betaine with methylation at individual cytosine-guanine dinucleotides (CpGs), and with median (genome-wide) methylation across all CpGs, CpGs in gene bodies, and CpGs in gene promoters. We also assessed associations with methylation at long interspersed nuclear element 1 (LINE-1), satellite 2 (Sat2), and Arthrobacter luteus restriction endonuclease (Alu) repetitive elements for a subset of participants. We used linear mixed regression, adjusting for age, sex, country of birth, smoking, energy intake from food, alcohol intake, Mediterranean diet score, and batch effects to assess log-linear associations with dietary intake of each nutrient. In secondary analyses, we assessed associations with low or high intakes defined by extreme quintiles. Results: No evidence of log-linear association was observed at P < 10-7 between the intake of one-carbon metabolism nutrients and methylation at individual CpGs. Low intake of riboflavin was associated with higher methylation at CpG cg21230392 in the first exon of PROM1 (P = 5.0 × 10-8). No consistent evidence of association was observed with genome-wide or repetitive element measures of methylation. Conclusion: Our findings suggest that dietary intake of one-carbon metabolism nutrients in adulthood, as measured by a food-frequency questionnaire, has little association with blood DNA methylation. An association with low intake of riboflavin requires replication in independent cohorts. This study was registered at http://www.clinicaltrials.gov as NCT03227003.

Shade Sails and Passive Recreation in Public Parks of Melbourne and Denver: A Randomized Intervention.

OBJECTIVES: To test whether shade sails will increase the use of passive recreation areas (PRAs). METHODS: We conducted a stratified randomized pretest-posttest controlled design study in Melbourne, Australia, and Denver, Colorado, in 2010 to 2014. We randomized a sample of 144 public parks with 2 PRAs in full sun in a 1:3 ratio to treatment or control. Shade sails were built at 1 PRA per treatment park. The outcome was any use of the study PRA (n = 576 pretest and n = 576 posttest observations; 100% follow-up). RESULTS: Compared with control PRAs (adjusted probability of use: pretest = 0.14, posttest = 0.17), use of treatment PRAs (pretest = 0.10, posttest = 0.32) was higher at posttest (odds ratio [OR] = 3.91; 95% confidence interval [CI] = 1.71, 8.94). Shade increased use of PRAs in Denver (control: pretest = 0.18, posttest = 0.19; treatment: pretest = 0.16, posttest = 0.47) more than Melbourne (control: pretest = 0.11, posttest = 0.14; shaded: pretest = 0.06, posttest = 0.19; OR = 2.98; 95% CI = 1.09, 8.14). CONCLUSIONS: Public investment in shade is warranted for skin cancer prevention and may be especially useful in the United States. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02971709.

Development of an online intervention for bipolar disorder. www.moodswings.net.au.

We describe the development process and completed structure, of a self-help online intervention for bipolar disorder, known as MoodSwings ( www.moodswings.net.au) . The MoodSwings program was adapted as an Internet intervention from an efficacious and validated face-to-face, group-based psychosocial intervention. The adaptation was created by a psychologist, who had previously been involved with the validation of the face-to-face program, in collaboration with website designers. The project was conducted under the supervision of a team of clinician researchers. The website is available at no cost to registered participants. Self-help modules are accessed sequentially. Other features include a mood diary and a moderated discussion board. There has been an average of 1,475,135 hits on the site annually (2008 and 2009), with some 7400 unique visitors each year. A randomised controlled trial based on this program has been completed. Many people with bipolar disorder are accepting of the Internet as a source of treatment and, once engaged, show acceptable retention rates. The Internet appears to be a viable means of delivering psychosocial self-help strategies.

Controlled clinical trial of a self-management program for people with mental illness in an adult mental health service - the Optimal Health Program (OHP).

OBJECTIVE: The objective of this study was to evaluate the effect and cost-effectiveness of a self-management intervention, delivered as part of routine care in an adult mental health service. METHOD: In a community mental health setting, routine care was compared with routine care plus a nine-session intervention (the Optimal Health Program) using a non-randomised controlled design. Adult (18-65 years) consumers of mental health services in the Australian Capital Territory were eligible for participation. RESULTS: The Optimal Health Program was associated with significant improvements in health and social functioning as measured by the Health of the Nation Outcome Scale (average change relative to control: -3.17; 95% CI -4.49 to -1.84; P<0.001). In addition, there was a reduction in hospital admissions in the treatment group (percentage of time in hospital reduced from 3.20 to 0.82; P=0.07). This translated into a net cost saving of over AU$6000 per participant per year (uncertainty range AU$744 to AU$12656). CONCLUSIONS: This study shows promising results for incorporating a self-management program into routine care to improve the health and social functioning of mental health consumers in a cost-effective manner.