Individual and area level factors associated with the breast cancer diagnostic-treatment interval in Queensland, Australia.

BACKGROUND: Delays to breast cancer treatment can lead to more aggressive and extensive treatments, increased expenses, increased psychological distress, and poorer survival. We explored the individual and area level factors associated with the interval between diagnosis and first treatment in a population-based cohort in Queensland, Australia. METHODS: Data from 3216 Queensland women aged 20 to 79, diagnosed with invasive breast cancer (ICD-O-3 C50) between March 2010 and June 2013 were analysed. Diagnostic dates were sourced from the Queensland Cancer Registry and treatment dates were collected via self-report. Diagnostics-treatment intervals were modelled using flexible parametric survival methods. RESULTS: The median interval between breast cancer diagnosis and first treatment was 15 days, with an interquartile range of 9-26 days. Longer diagnostic-treatment intervals were associated with a lack of private health coverage, lower pre-diagnostic income, first treatments other than breast conserving surgery, and residence outside a major city. The model explained a modest 13.7% of the variance in the diagnostic-treatment interval [Formula: see text]. Sauerbrei's D was 0.82, demonstrating low to moderate discrimination performance. CONCLUSION: Whilst this study identified several individual- and area-level factors associated with the time between breast cancer diagnosis and first treatment, much of the variation remained unexplained. Increased socioeconomic disadvantage appears to predict longer diagnostic-treatment intervals. Though some of the differences are small, many of the same factors have also been linked to screening and diagnostic delay. Given the potential for accumulation of delay at multiple stages along the diagnostic and treatment pathway, identifying and applying effective strategies address barriers to timely health care faced by socioeconomically disadvantaged women remains a priority.

Development of a key performance indicator for breast cancer in Queensland, Australia.

PURPOSE: Using population-based data for women diagnosed with stage I-III breast cancer, our aim was to examine the impact of time to treatment completion on survival and to identify factors associated with treatment delay. METHODS: This retrospective study used clinical and treatment data from the Queensland Oncology Repository. Time from diagnosis to completing surgery, chemotherapy and radiation therapy identified a cut-off of 37 weeks as the optimal threshold for completing treatment. Logistic regression was used to identify factors associated with the likelihood of completing treatment > 37 weeks. Overall (OS) and breast cancer-specific survival (BCSS) were examined using Cox proportional hazards models. RESULTS: Of 8279 women with stage I-III breast cancer, 31.9% completed treatment > 37 weeks. Apart from several clinical factors, being Indigenous (p = 0.002), living in a disadvantaged area (p = 0.003) and receiving ≥ two treatment modalities within the public sector (p < 0.001) were associated with an increased likelihood of completing treatment > 37 weeks. The risk of death from any cause was about 40% higher for women whose treatment went beyond 37 weeks (HR 1.37, 95%CI 1.16-1.61), a similar result was observed for BCSS. Using the surgery + chemotherapy + radiation pathway, a delay of > 6.9 weeks from surgery to starting chemotherapy was significantly associated with poorer survival (p = 0.001). CONCLUSIONS: Several sociodemographic and system-related factors were associated with a greater likelihood of treatment completion > 37 weeks. We are proposing a key performance indicator for the management of early breast cancer where a facility should have > 90% of patients with a time from surgery to adjuvant chemotherapy < 6.9 weeks.

Trends in surgery and adjuvant treatment for early-stage breast cancer: a population-based study in Queensland, Australia.

PURPOSE: Our aim was to describe variations in the treatment of early-stage breast cancer and to examine factors associated with disease-specific survival (DSS). METHODS: The study used linked data for 24,190 women with a T1 (≤ 20 mm) breast cancer who underwent surgery from 2005 to 2019. Multivariate logistic regression was used to model predictors of receiving breast-conserving surgery (BCS) compared to mastectomy and a multinomial model was used to examine factors associated with type(s) of treatment received. RESULTS: Overall, 70.3% had BCS, with a reduced likelihood of BCS observed for younger women (p < 0.001), rural residence, (p < 0.001), socioeconomic disadvantage (p = 0.004), higher tumour grade (p < 0.001) and surgery in a public versus private hospital (p < 0.001). Compared to women who received BCS and radiation therapy (RT), those having mastectomy alone or mastectomy plus RT were more likely to be younger (p < 0.001), live in a rural area (p < 0.001), have higher-grade tumours (p < 0.001) and positive lymph nodes (p < 0.001). Overall 5-year survival was 95.3% and breast cancer-specific survival was 98.3%. Highest survival was observed for women having BCS and RT and lowest for those having mastectomy and RT (p < 0.001). CONCLUSION: Our results indicate some variation in the management of early-stage breast cancer. Lower rates of BCS were observed for rural and disadvantaged women and for those treated in a public or low-volume hospital. Whilst survival was high for this cohort, differences in tumour biology likely explain the differences in survival according to treatment type.

Supportive care needs and psychosocial outcomes of rural versus urban women with breast cancer.

OBJECTIVE: To identify whether supportive care needs vary according to remoteness and area-level socio-economic status and to identify the combinations of socio-demographic, area-level and health factors that are associated with poorer quality of life, psychological distress and severity of unmet supportive care needs. METHODS: Cross sectional data was collected from women with a breast cancer diagnosis (n = 2635) in Queensland, Australia, through a telephone survey including socio-demographic, health, psychosocial and supportive care needs measures. Hierarchical regression and cluster analyses were applied to assess the predictors of unmet need and psychosocial outcomes and to identify socio-demographic and health status profiles of women, comparing their level of unmet needs and psychosocial outcomes. RESULTS: Women living in outer regional areas reported the highest severity of unmet need in the patient care domain. Greater unmet need for health systems and information and patient care was also evident for those in moderately and most disadvantaged areas. Three clusters were identified reflecting (1) older women with poorer health and lower education (19%); (2) younger educated women with better health and private insurance (61%); and (3) physically active women with localised cancer who had completed treatment (20%). Poorer outcomes were evident in the first two of these clusters. CONCLUSIONS: This better understanding of the combinations of characteristics associated with poorer psychosocial outcomes and higher unmet need can be used to identify women with higher supportive care needs early and to target interventions.

Tobacco smoking and risk of thyroid cancer according to BRAFV600E mutational subtypes.

OBJECTIVE: Smoking has been associated with a reduced risk of thyroid cancer, but whether the association varies between higher- and lower-risk cancers remains unclear. We aimed to assess the association between smoking and risk of thyroid cancer overall as well as by tumour BRAF mutational status as a marker of potentially higher-risk cancer. DESIGN AND PATIENTS: We recruited 1013 people diagnosed with thyroid cancer and 1057 population controls frequency-matched on age and sex. METHODS: Multivariable logistic regression was used to assess the association overall and in analyses stratified by tumour characteristics. We used sensitivity analysis to assess the potential for selection bias. RESULTS: We found little evidence of an association with current smoking (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.69-1.26; current vs. never smoking), but a higher number of pack-years of smoking was associated with a lower risk of thyroid cancer (OR = 0.75; 95% CI: 0.57-0.99; ≥20 pack-years vs. never). However, after correcting for potential selection bias, we observed a statistically significant inverse association between current smoking and risk of thyroid cancer (bias-corrected OR = 0.65; 95% CI: 0.51-0.83). Those with BRAF-positive cancers were less likely to be current smokers than those with BRAF-negative cancers (prevalence ratio: 0.79; 95% CI: 0.62-0.99). CONCLUSION: We found smoking was inversely related to thyroid cancer risk and, in particular, current smoking was associated with a reduced risk of potentially more aggressive BRAF-positive than the likely more indolent BRAF-negative papillary thyroid cancers.

Nonbreast cancer incidence, treatment received and outcomes: Are there differences in breast screening attendees versus nonattendees?

While reductions in breast cancer mortality have been evident since the introduction of population-based breast screening in women aged 50-74 years, participation in cancer screening programs can be influenced by several factors, including health system and those related to the individual. In our study, we compared cancer incidence and mortality for several cancer types other than breast cancer, noncancer mortality and patterns of treatment amongst women who did and did not participate in mammography screening. All women aged 50-65 years enrolled on the Queensland Electoral Roll in 2000 were included. The study population was then linked to records from the population-based breast screening program and private fee-for-service screening options to establish screened and unscreened cohorts. Diagnostic details for selected cancers and cause of death were obtained from the Queensland Oncology Repository. We calculated incidence rate ratios and hazard ratios comparing screened and unscreened cohorts. Among screened compared to unscreened women, we found a lower incidence of cancers of the lung, cervix, head and neck and esophagus and an increase in colorectal cancers. Cancer mortality (excluding breast cancer) was 35% lower among screened compared to unscreened women and they were also about 23% less likely to be diagnosed with distant disease. Screened compared to unscreened women were more likely to receive surgery and less likely to receive no treatment. Our study adds further to the population data examining outcomes among women participating in mammography screening.

Factors associated with being diagnosed with high severity of breast cancer: a population-based study in Queensland, Australia.

PURPOSE: This study explores factors that are associated with the severity of breast cancer (BC) at diagnosis. METHODS: Interviews were conducted among women (n = 3326) aged 20-79 diagnosed with BC between 2011 and 2013 in Queensland, Australia. High-severity cancers were defined as either Stage II-IV, Grade 3, or having negative hormone receptors at diagnosis. Logistic regression models were used to estimate odds ratios (ORs) of high severity BC for variables relating to screening, lifestyle, reproductive habits, family history, socioeconomic status, and area disadvantage. RESULTS: Symptom-detected women had greater odds (OR 3.38, 2.86-4.00) of being diagnosed with high-severity cancer than screen-detected women. Women who did not have regular mammograms had greater odds (OR 1.78, 1.40-2.28) of being diagnosed with high-severity cancer than those who had mammograms biennially. This trend was significant in both screen-detected and symptom-detected women. Screen-detected women who were non-smokers (OR 1.77, 1.16-2.71), postmenopausal (OR 2.01, 1.42-2.84), or employed (OR 1.46, 1.15-1.85) had greater odds of being diagnosed with high-severity cancer than those who were current smokers, premenopausal, or unemployed. Symptom-detected women being overweight (OR 1.67, 1.31-2.14), postmenopausal (OR 2.01, 1.43-2.82), had hormone replacement therapy (HRT) < 2 years (OR 1.60, 1.02-2.51) had greater odds of being diagnosed with high-severity cancer than those of healthy weight, premenopausal, had HRT > 10 years. CONCLUSION: Screen-detected women and women who had mammograms biennially had lower odds of being diagnosed with high-severity breast cancer, which highlighted the benefit of regular breast cancer screening. Women in subgroups who are more likely to have more severe cancers should be particularly encouraged to participate in regular mammography screening.

A prospective and population-based inquiry on the use and acceptability of peer support for women newly diagnosed with breast cancer.

The degree to which peer support is used and accepted as a supportive care approach by women with breast cancer is unclear. We examine peer support use across three major modalities (i.e. support groups, online platforms, one-on-one) and identify enablers and barriers to peer support using the beliefs framework of the theory of planned behaviour. A population-based sample of women newly diagnosed with breast cancer (n = 3105) who were on average 54.08 weeks since diagnosis completed mailed surveys at baseline measuring beliefs about peer support and intention. Peer support use was measured via telephone interview at baseline and prospectively at 12-month follow-up (n = 2780). In all, 37% of women had used at least one peer support service since diagnosis (support group = 20%, online = 18%, one-on-one = 10%). A path analysis examined what beliefs enabled or acted as barriers to peer support use at follow-up adjusting for past behaviour (i.e. baseline use), sociodemographic characteristics, and treatment. In order of relative strength, enablers included beliefs that peer support is an outlet for honest expression of feelings (ß = .35), a source of empathy (ß = .30), approved by doctors (ß = .07), and approved by family/partner (ß = .04). Barriers were beliefs that it encourages dwelling about breast cancer (ß = - .06) and involves exposure to negative stories about this disease (ß = - .04). Strategies which communicate the potential emotional support benefits of a shared illness experience and social approval by others, particularly the medical profession, may help to promote acceptance of peer support and encourage service uptake in breast cancer.

What factors influence the treatment decisions of women with breast cancer? Does residential location play a role?

INTRODUCTION: Inequalities in cancer outcomes continue to exist throughout the world. In Australia, rural women diagnosed with breast cancer have significantly poorer 5-year survival, with variations in clinical management additionally observed. While factors impacting clinical management have been identified, there is little understanding about the factors that influence treatment decisions of women diagnosed with breast cancer. METHODS: A mixed-methods study was conducted with women diagnosed with either pre-invasive or invasive breast cancer in Australia. The study included qualitative interviews and an online survey utilising Breast Cancer Network Australia's membership. Semi-structured interviews were conducted with rural women focusing on topics such as decision-making and factors influencing this. The online survey amongst metropolitan and rural (including regional, remote, very remote) women examined involvement in, and preference for, decision-making, and to what degree certain factors influenced treatment decisions. Sociodemographics included age, residential location, education and household income. Qualitative interviews were analysed using NVivo, and descriptive analyses were used to examine differences in frequency distributions across survey questions by residential location and age group for the online survey. Multivariable logistic regression analysis was conducted to examine factors associated with treatment decision-making. RESULTS: Nine women participated in the qualitative interviews and 815 (365 metropolitan and 450 rural) completed the online survey. Interviews found most women concurred with the recommendations of their doctor(s) and did not see this experience as 'making a decision'. In the online survey, 83.2% of women indicated at least some involvement in the decision-making with this being similar between rural and metropolitan women. Compared to women educated at an under- or postgraduate level, those educated at high school or less were about 50% less likely to be involved in treatment decision(s) (OR=0.51, 95% confidence interval=0.30-0.86). In both interviews and the online survey, factors having the strongest influence on treatment decisions centred around survival and reducing risk of progression or recurrence. Significantly more rural compared to metropolitan women indicated their decision was strongly influenced by treatment service location (42.8% and 28.1%, respectively, p<0.001). Rural women more frequently cited financial costs of treatment influenced their decision compared to metropolitan women (30.4% and 21.3%, respectively, p=0.04). Significantly fewer rural, (16.2%) compared to metropolitan (23.6%) women, had breast reconstruction (p=0.009). The option of having reconstructive surgery was less frequently cited as influencing treatment decisions for rural compared to metropolitan women (27.7% v 44.1% respectively, p<0.001). CONCLUSIONS: The treatment decisions of the majority of women were strongly influenced by the need to do everything possible to get better; however, rural women additionally indicated their decisions were also influenced by factors such as access to treatment services and the financial costs of treatment. Addressing travel and costs issues for rural women with breast cancer should be prioritised. Additionally, the finding that women with lower levels of education were significantly less likely to be involved in the decision-making process highlights the need to develop new or tailor existing resources. Further work could also examine the reasons why rural women are less likely to consider breast reconstruction important in decision-making.

Web-Delivered Cognitive Behavioral Therapy for Distressed Cancer Patients: Randomized Controlled Trial.

BACKGROUND: Web-based interventions present a potentially cost-effective approach to supporting self-management for cancer patients; however, further evidence for acceptability and effectiveness is needed. OBJECTIVE: The goal of our research was to assess the effectiveness of an individualized Web-based cognitive behavioral therapy (CBT) intervention on improving psychological and quality of life outcomes in cancer patients with elevated psychological distress. METHODS: A total of 163 distressed cancer patients (111 female, 68.1%) were recruited through the Queensland Cancer Registry and the Cancer Council Queensland Cancer Helpline and randomly assigned to either a Web-based tailored CBT intervention (CancerCope) (79/163) or a static patient education website (84/163). At baseline and 8-week follow-up we assessed primary outcomes of psychological and cancer-specific distress and unmet psychological supportive care needs and secondary outcomes of positive adjustment and quality of life. RESULTS: Intention-to-treat analyses showed no evidence of a statistically significant intervention effect on primary or secondary outcomes. However, per-protocol analyses found a greater decrease for the CancerCope group in psychological distress (P=.04), cancer-specific distress (P=.02), and unmet psychological care needs (P=.03) from baseline to 8 weeks compared with the patient education group. Younger patients were more likely to complete the CancerCope intervention. CONCLUSIONS: This online CBT intervention was associated with greater decreases in distress for those patients who more closely adhered to the program. Given the low costs and high accessibility of this intervention approach, even if only effective for subgroups of patients, the potential impact may be substantial. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613001026718; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364768&isReview=true (Archived by WebCite at http://www.webcitation.org/6uPvpcovl).

Google as a cancer control tool in Queensland.

BACKGROUND: Recent advances in methodologies utilizing "big data" have allowed researchers to investigate the use of common internet search engines as a real time tool to track disease. Little is known about its utility with tracking cancer incidence. This study aims to investigate the potential correlates of monthly internet search volume indexes (SVIs) and observed monthly age standardised incidence rates (ASRs) for breast cancer, colorectal cancer, melanoma and prostate cancer. METHODS: The monthly ASRs for the four cancers in Queensland were calculated using data from the Queensland Cancer Registry between January 2006 and December 2012. The monthly SVIs of the respective cancer search terms in Queensland were accessed from Google Trends for the same period. A time series seasonal decomposition method was performed to detect the seasonal patterns of SVIs and ASRs. Pearson's correlation coefficient and time series cross-correlation analysis were used to assess the associations between SVIs and ASRs. Linear regression models were used to examine the power of SVIs to predict monthly in ASRs. RESULTS: Increases in the monthly ASRs of the four cancers were significantly correlated with increases in the monthly SVIs of the respective cancers except for colorectal cancer. The predictive power of the SVIs to explain variances in the corresponding ASRs varied by cancer type, with the percent explained ranging from 5.6% for breast cancer to 17.9% for skin cancer (SVI) with melanoma (ASR). Some improvement in the variation explained was obtained by including more search terms or lagged SVIs for the respective cancers in the linear regression models. The seasonal analysis indicated that the SVIs peaked periodically at around their respective cancer awareness months. CONCLUSIONS: Using SVIs from a popular internet search engine was only able to explain a small portion of changes in the respective ASRs. While an expanded regression model explained a higher proportion of variability, the interpretation of this was difficult. Further development and refinement of this approach will be needed before search-based cancer surveillance can provide useful information regarding resource deployment to guide cancer control and track the impact of cancer awareness and education programmes.

Cost-Effectiveness Analysis of a Skin Awareness Intervention for Early Detection of Skin Cancer Targeting Men Older Than 50 Years.

OBJECTIVES: To assess the cost-effectiveness of an educational intervention encouraging self-skin examinations for early detection of skin cancers among men older than 50 years. METHODS: A lifetime Markov model was constructed to combine data from the Skin Awareness Trial and other published sources. The model incorporated a health system perspective and the cost and health outcomes for melanoma, squamous and basal cell carcinomas, and benign skin lesions. Key model outcomes included Australian costs (2015), quality-adjusted life-years (QALYs), life-years, and counts of skin cancers. Univariate and probabilistic sensitivity analyses were undertaken to address parameter uncertainty. RESULTS: The mean cost of the intervention was A$5,298 compared with A$4,684 for usual care, whereas mean QALYs were 7.58 for the intervention group and 7.77 for the usual care group. The intervention was thus inferior to usual care. When only survival gain is considered, the model predicted the intervention would cost A$1,059 per life-year saved. The likelihood that the intervention was cost-effective up to A$50,000 per QALY gained was 43.9%. The model was stable to most data estimates; nevertheless, it relies on the specificity of clinical diagnosis of skin cancers and is subject to limited health utility data for people with skin lesions. CONCLUSIONS: Although the intervention improved skin checking behaviors and encouraged men to seek medical advice about suspicious lesions, the overall costs and effects from also detecting more squamous and basal cell carcinomas and benign lesions outweighed the positive health gains from detecting more thin melanomas.

Temporal changes in loss of life expectancy due to cancer in Australia: a flexible parametric approach.

PURPOSE: To evaluate changes in cancer mortality burden over time by assessing temporal trends in life expectation for Australian residents diagnosed with cancer. METHODS: The study cohort consisted of all people diagnosed with cancer in the period 1990-2000 and aged 15-89 years (n = 1,275,978), with mortality follow-up to 31 December 2010. Flexible parametric survival models incorporating background age-sex-year-specific population mortality rates were applied to generate the observed survival curves for all cancers combined and selected major cancer types. Predicted values of loss of life expectancy (LOLE) in years were generated and then averaged across calendar year and age group (15-49, 50-69 and 70-89 years) or spread of disease (localized, regional, distant, unknown). RESULTS: The greatest LOLE burden was for lung cancer (14.3 years per diagnosis) and lowest for melanoma (2.5 years). There was a significant decrease in LOLE over time (-0.13 LOLE per year) for all cancers combined. Decreases were also observed for female breast cancer (-0.21), prostate cancer (-0.17), colorectal cancer (-0.08), melanoma (-0.07) and stomach cancer (-0.02), with slight increases for lung cancer (+0.04). When restricted to the sub-cohort from New South Wales with spread of disease information, these decreases in LOLE were primarily among cancers categorized as localized or regional spread at diagnosis. CONCLUSIONS: In Australia, persons diagnosed with cancer have a steadily improving outlook that exceeds that expected by general improvement in population life expectancy. The overall improvement is observed in persons with localized or regional cancers but not in those with advanced cancers, findings which encourage earlier diagnosis.

Mediation of improvements in sun protective and skin self-examination behaviours: results from the healthy text study.

OBJECTIVE: Melanoma is on the rise, especially in Caucasian populations exposed to high ultraviolet radiation such as in Australia. This paper examined the psychological components facilitating change in skin cancer prevention or early detection behaviours following a text message intervention. METHODS: The Queensland-based participants were 18 to 42 years old, from the Healthy Text study (N = 546). Overall, 512 (94%) participants completed the 12-month follow-up questionnaires. Following the social cognitive model, potential mediators of skin self-examination (SSE) and sun protection behaviour change were examined using stepwise logistic regression models. RESULTS: At 12-month follow-up, odds of performing an SSE in the past 12 months were mediated by baseline confidence in finding time to check skin (an outcome expectation), with a change in odds ratio of 11.9% in the SSE group versus the control group when including the mediator. Odds of greater than average sun protective habits index at 12-month follow-up were mediated by (a) an attempt to get a suntan at baseline (an outcome expectation) and (b) baseline sun protective habits index, with a change in odds ratio of 10.0% and 11.8%, respectively in the SSE group versus the control group. CONCLUSIONS: Few of the suspected mediation pathways were confirmed with the exception of outcome expectations and past behaviours. Future intervention programmes could use alternative theoretical models to elucidate how improvements in health behaviours can optimally be facilitated.

Diagnosis of an additional in situ melanoma does not influence survival for patients with a single invasive melanoma: A registry-based follow-up study.

Using a large (N= 25 493) population-based cohort from Queensland, Australia, we compared melanoma survival among cases with a single invasive melanoma only against those who also had a diagnosis of a single in situ melanoma. After adjustment for sex, age, body site, clinicopathological subtype, thickness and ulceration, it was found that there was no difference (P = 0.99) in 10-year melanoma-specific mortality following a diagnosis of an invasive lesion, whether or not an in situ melanoma was also present. We conclude that in situ melanomas do not alter the prognosis of an invasive melanoma.

Outdoor workers and sun protection strategies: two case study examples in Queensland, Australia.

INTRODUCTION: Outdoor workers are at risk of developing skin cancer because they are exposed to high levels of harmful ultraviolet radiation. The Outdoor Workers Sun Protection Project investigated sun protection strategies for high risk outdoor workers in rural and regional Australia. METHODS: Fourteen workplaces (recruitment rate 37%) across four industries in rural and regional Queensland, Australia were recruited to the OWSPP. In 2011-2012, data were collected using pre- and post-intervention interviews and discussion groups. This article presents two workplaces as case study examples. RESULTS: The flat organisational structure of workplace 1 supported the implementation of the Sun Safety Action Plan (SSAP), whilst the hierarchical organisational nature of workplace 2 delayed implementation of the SSAP. Neither workplace had an existing sun protection policy but both workplaces adopted one. An effect related to the researchers' presence was seen in workplace 1 and to a lesser degree in workplace 2. Overt reciprocity was seen between management and workers in workplace 1 but this was not so evident in workplace 2. In both workplaces, the role of the workplace champion was pivotal to SSAP progression. CONCLUSIONS: These two case studies highlight a number of contextually bound workplace characteristics related to sun safety. These issues are (1) the structure of workplace, (2) policy, (3) an effect related to the researchers' presence, (4) the workplace champion and (5) reciprocity. There are several recommendations from this article. Workplace health promotion strategies for sun safety need to be contextualised to individual workplaces to take advantage of the strengths of the workplace and to build capacity.

Genetic association analysis of miRNA SNPs implicates MIR145 in breast cancer susceptibility.

BACKGROUND: MicroRNAs (miRNAs) are important small non-coding RNA molecules that regulate gene expression in cellular processes related to the pathogenesis of cancer. Genetic variation in miRNA genes could impact their synthesis and cellular effects and single nucleotide polymorphisms (SNPs) are one example of genetic variants studied in relation to breast cancer. Studies aimed at identifying miRNA SNPs (miR-SNPs) associated with breast malignancies could lead towards further understanding of the disease and to develop clinical applications for early diagnosis and treatment. METHODS: We genotyped a panel of 24 miR-SNPs using multiplex PCR and chip-based matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) analysis in two Caucasian breast cancer case control populations (Primary population: 173 cases and 187 controls and secondary population: 679 cases and 301 controls). Association to breast cancer susceptibility was determined using chi-square (X (2) ) and odds ratio (OR) analysis. RESULTS: Statistical analysis showed six miR-SNPs to be non-polymorphic and twelve of our selected miR-SNPs to have no association with breast cancer risk. However, we were able to show association between rs353291 (located in MIR145) and the risk of developing breast cancer in two independent case control cohorts (p = 0.041 and p = 0.023). CONCLUSIONS: Our study is the first to report an association between a miR-SNP in MIR145 and breast cancer risk in individuals of Caucasian background. This finding requires further validation through genotyping of larger cohorts or in individuals of different ethnicities to determine the potential significance of this finding as well as studies aimed to determine functional significance.

Association of microRNA 17-92 cluster host gene (MIR17HG) polymorphisms with breast cancer.

Breast cancer incidence and mortality rates are increasing despite our current knowledge on the disease. Ninety-five percent of breast cancer cases correspond to sporadic forms of the disease and are believed to involve an interaction between environmental and genetic determinants. The microRNA 17-92 cluster host gene (MIR17HG) has been shown to regulate expression of genes involved in breast cancer development and progression. Study of single-nucleotide polymorphisms (SNPs) located in this cluster gene could help provide a further understanding of its role in breast cancer. Therefore, this study investigated six SNPs in the MIR17HG using two independent Australian Caucasian case-control populations (GRC-BC and GU-CCQ BB populations) to determine association to breast cancer susceptibility. Genotyping was undertaken using chip-based matrix assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry (MS). We found significant association between rs4824505 and breast cancer at the allelic level in both study cohorts (GRC-BC p = 0.01 and GU-CCQ BB p = 0.03). Furthermore, haplotypic analysis of results from our combined population determined a significant association between rs4824505/rs7336610 and breast cancer susceptibility (p = 5 × 10(-4)). Our study is the first to show that the A allele of rs4824505 and the AC haplotype of rs4824505/rs7336610 are associated with risk of breast cancer development. However, definitive validation of this finding requires larger cohorts or populations in different ethnical backgrounds. Finally, functional studies of these SNPs could provide a deeper understanding of the role that MIR17HG plays in the pathophysiology of breast cancer.

Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population.

Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.

Psychological distress and quality of life in lung cancer: the role of health-related stigma, illness appraisals and social constraints.

OBJECTIVE: Health-related stigma is associated with negative psychological and quality of life outcomes in lung cancer patients. This study describes the impact of stigma on lung cancer patients' psychological distress and quality of life and explores the role of social constraints and illness appraisal as mediators of effect. METHODS: A self-administered cross-sectional survey examined psychological distress and quality of life in 151 people (59% response rate) diagnosed with lung cancer from Queensland and New South Wales. Health-related stigma, social constraints and illness appraisals were assessed as predictors of adjustment outcomes. RESULTS: Forty-nine percent of patients reported elevated anxiety; 41% were depressed; and 51% had high global distress. Health-related stigma was significantly related to global psychological distress and quality of life with greater stigma and shame related to poorer outcomes. These effects were mediated by illness appraisals and social constraints. CONCLUSIONS: Health-related stigma appears to contribute to poorer adjustment by constraining interpersonal discussions about cancer and heightening feelings of threat. There is a need for the development and evaluation of interventions to ameliorate the negative effects of health-related stigma among lung cancer patients.