MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer.

Background: MSR1 repeats are a 36-38 bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV). Patients and methods: Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer. Results: MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1 and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P = 4.80 × 10-7) and ion channel activity (P = 2.7 × 10-4). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9 and 11 copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P = 0.004; P = 0.03). In the white British population, the minor allele conferred an increased risk of 1.21-3.51 times for all non-familial disease, or 1.7-5.3 times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27-1.56; P =0.009). Conclusions: MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Advocacy, support and survivorship in prostate cancer.

Across Australia, prostate cancer support groups (PCSG) have emerged to fill a gap in psychosocial care for men and their families. However, an understanding of the triggers and influencers of the PCSG movement is absent. We interviewed 21 SG leaders (19 PC survivors, two partners), of whom six also attended a focus group, about motivations, experiences, past and future challenges in founding and leading PCSGs. Thematic analysis identified four global themes: illness experience; enacting a supportive response; forming a national collective and challenges. Leaders described men's feelings of isolation and neglect by the health system as the impetus for PCSGs to form and give/receive mutual help. Negotiating health care systems was an early challenge. National affiliation enabled leaders to build a united voice in the health system and establish a group identity and collective voice. Affiliation was supported by a symbiotic relationship with tensions between independence, affiliation and governance. Future challenges were group sustainability and inclusiveness. Study findings describe how a grassroots PCSG movement arose consistent with an embodied health movement perspective. Health care organisations who seek to leverage these community resources need to be cognisant of SG values and purpose if they are to negotiate effective partnerships that maximise mutual benefit.

"Prostate cancer is far more hidden ": Perceptions of stigma, social isolation and help-seeking among men with prostate cancer.

The purpose of this study was to provide in-depth insight into men's experiences of prostate cancer, specifically: perceived stigma and self-blame, social isolation, unmet need and help-seeking. A qualitative descriptive approach was used. Semi-structured interviews were undertaken with 20 men diagnosed with prostate cancer, and thematic analysis was undertaken. Some participants perceived a stigma associated with prostate cancer and cancer in general, which sometimes acted as a barrier to disclosure. Self-blame and internalisation of cause was not a prominent issue. Participants' descriptions of emotional distress, social isolation and anxiety demonstrated the impact of prostate cancer. Social isolation was most commonly reported as a physical consequence of treatment and/or side effects. Participants felt both support and ongoing care were limited at post-treatment. Most did not seek or receive help for emotional or psychosocial problems from a formal source due to anticipated awkwardness, autonomous coping, not burdening others, unwanted sympathy and retaining privacy. Prostate cancer can cause considerable emotional and social burden for some men, and many are unlikely to seek or receive help. Men, and their support networks, require active encouragement throughout diagnosis, treatment and follow-up to overcome barriers and access additional support, particularly for sexual, emotional and psychosocial issues.

Financial toxicity: a potential side effect of prostate cancer treatment among Australian men.

The purpose of this study was to understand the extent, nature and variability of the current economic burden of prostate cancer among Australian men. An online cross-sectional survey was developed that combined pre-existing economic measures and new questions. With few exceptions, the online survey was viable and acceptable to participants. The main outcomes were self-reported out-of-pocket costs of prostate cancer diagnosis and treatment, changes in employment status and household finances. Men were recruited from prostate cancer support groups throughout Australia. Descriptive statistical analyses were undertaken. A total of 289 men responded to the survey during April and June 2013. Our study found that men recently diagnosed (within 16 months of the survey) (n = 65) reported spending a median AU$8000 (interquartile range AU$14 000) for their cancer treatment while 75% of men spent up to AU$17 000 (2012). Twenty per cent of all men found the cost of treating their prostate cancer caused them 'a great deal' of distress. The findings suggest a large variability in medical costs for prostate cancer treatment with 5% of men spending $250 or less in out-of-pocket expenses and some men facing very high costs. On average, respondents in paid employment at diagnosis stated that they had retired 4-5 years earlier than planned.

Men's help-seeking in the first year after diagnosis of localised prostate cancer.

This study describes sources of support utilised by men with localised prostate cancer in the first year after diagnosis and examines characteristics associated with help-seeking for men with unmet needs. A cross-sectional survey of 331 patients from a population-based sample who were in the first year after diagnosis (M = 9.6, SD = 1.9) was conducted to assess sources of support, unmet supportive care needs, domain-specific quality of life and psychological distress. Overall, 82% of men reported unmet supportive care needs. The top five needs were sexuality (58%); prostate cancer-specific (57%); psychological (47%); physical and daily living (41%); and health system and information (31%). Professional support was most often sought from doctors (51%). Across most domains, men who were older (Ps ≤ 0.03), less well educated (Ps ≤ 0.04) and more depressed (Ps ≤ 0.05) were less likely to seek help for unmet needs. Greater sexual help-seeking was related to better sexual function (P = 0.03), higher education (P ≤ 0.03) and less depression (P = 0.05). Unmet supportive care needs are highly prevalent after localised prostate cancer diagnosis with older age, lower education and higher depression apparent barriers to help-seeking. Interventions that link across medicine, nursing and community based peer support may be an accessible approach to meeting these needs. Clinical Trial Registry: Trial Registration: ACTRN12611000392965.

Associations between aerobic exercise levels and physical and mental health outcomes in men with bone metastatic prostate cancer: a cross-sectional investigation.

Cancer patients with bone metastases have previously been excluded from participation in physical activity programmes due to concerns of skeletal fractures. Our aim was to provide initial information on the association between physical activity levels and physical and mental health outcomes in prostate cancer patients with bone metastases. Between 2012 and 2015, 55 prostate cancer patients (mean age 69.7 ± 8.3; BMI 28.6 ± 4.0) with bone metastases (58.2% >2 regions affected) undertook assessments for self-reported physical activity, physical and mental health outcomes (SF-36), objective physical performance measures and body composition by DXA. Sixteen men (29%) met the current aerobic exercise guidelines for cancer survivors, while 39 (71%) reported lower aerobic exercise levels. Men not meeting aerobic exercise guidelines had lower physical functioning (p = .004), role functioning (physical and emotional) (p < .05), general health scores (p = .014) as well all lower measures of physical performance (p < .05). Lower levels of aerobic exercise are associated with reduced physical and mental health outcomes in prostate cancer patients with bone metastases. While previous research has focused primarily in those with non-metastatic disease, our initial results suggest that higher levels of aerobic exercise may preserve physical and mental health outcomes in prostate cancer patients with bone metastases. Clinical Trial Registry: Trial Registration: ACTRN12611001158954.

An investigation of the emotion of disgust as an affective barrier to intention to screen for colorectal cancer.

Colorectal cancer (CRC) screening participation remains unacceptably low. This study investigated the emotion of disgust as a potential deterrent to intention to screen for CRC. The study utilised a convenience sample of individuals' 40-70 years of age to complete an online survey. Participants included 30 men and 118 women recruited between December 1, 2013 and March 31, 2014. Data on socio-demographics, health status, screening intentions and emotional barriers to bowel screening were collected via an on-line survey. Logistic regression analysis was utilised to investigate predictors of screening intention. Individuals were more likely to report intention to screen if they had prior screening experience, and reported fewer emotional concerns to screening for CRC. Results implicate disgust as a predictor of screening avoidance among participants. Specifically, higher reported faecal disgust was predictive of a 3% decrease in screening intention. This study was the first to empirically position disgust alongside other negative emotional states as an affective barrier to screening for CRC. Trait disgust sensitivity was not a reliable predictor of screening intention. This research suggests that anticipated faecal disgust may contribute to avoidance of screening for CRC.

Barriers to lung cancer care: health professionals' perspectives.

PURPOSE: Globally, lung cancer is the most common cancer and the leading cause of cancer death. Problematically, there is a wide variation in the management and survival for people with lung cancer and there is limited understanding of the reasons for these variations. To date, the views of health professionals across relevant disciplines who deliver such care are largely absent. The present study describes Australian health professionals' views about barriers to lung cancer care to help build a research and action agenda for improving lung cancer outcomes. METHODS: Qualitative semi-structured interviews were undertaken with a multidisciplinary group of 31 Australian health professionals working in lung cancer care for an average of 16 years (range 1-35 yrs.; SD = 10.2) seeing a mean of 116 patients annually. RESULTS: Three superordinate themes were identified: illness representations, cultural influences, and health system context. Illness representations included three themes: symptoms attributed as smoking-related but not cancer, health-related stigma, and therapeutic nihilism. Cultural influence themes included Indigenous health care preferences, language and communication, and sociodemographic factors. Health system context included lack of regional services and distance to treatment, poor care coordination, lack of effective screening methods, and health professional behaviours. CONCLUSIONS: Fractured and locally isolated approaches routinely confound responses to the social, cultural and health system complexities that surround a diagnosis of lung cancer and subsequent treatment. Improving outcomes for this disadvantaged patient group will require government, health agencies, and the community to take an aggressive, integrated approach balancing health policy, treatment priorities, and societal values.

Psycho-oncology assessment in Chinese populations: a systematic review of quality of life and psychosocial measures.

This systematic review describes psychosocial and quality of life (QOL) measures used in psycho-oncology research with cancer patients and caregivers in China. Medline and PsycINFO databases were searched (1980-2014). Studies reviewed met the following criteria: English language; peer-reviewed; sampled Chinese cancer patients/caregivers; developed, validated or assessed psychometric properties of psychosocial or QOL outcome measures; and reported validation data. The review examined characteristics of measures and participants, translation and cultural adaptation processes and psychometric properties of the measures. Ninety five studies met review criteria. Common characteristics of studies reviewed were they: assessed primarily QOL measures, sampled patients with breast, colorectal, or head and neck cancer, and validated existing measures (>80%) originating in North America or Europe. Few studies reported difficulties translating measures. Regarding psychometric properties of the measures >50% of studies reported subscale reliabilities <α = 0.70, <50% reported test-retest reliability, and <30% reported divergent validity. Few reported sensitivity, specificity or responsiveness. Improved accuracy and transparency of reporting for translation, cultural adaptation and psychometric testing of psychosocial measures is needed. Developing support structures for translating and validating psychosocial measures would enable this and ensure Chinese psycho-oncology clinical practice and research keeps pace with international focus on patient reported outcome measures and data management.

Psychological wellness and health-related stigma: a pilot study of an acceptance-focused cognitive behavioural intervention for people with lung cancer.

People with lung cancer experience health-related stigma that is related to poorer psychosocial and quality of life outcomes. The present Phase 1 study applied mixed methods to test the acceptability of an acceptance-focused cognitive behavioural intervention targeting stigma for this patient group. Fourteen lung cancer patients completed a 6-week Psychological Wellness intervention with pre- and post-test outcome measures of psychological and cancer-specific distress, depression, health-related stigma and quality of life. In-depth interviews applying interpretative phenomenological analysis assessed participants' experiences of the intervention. Moderate to large improvements were observed in psychological (ηp (2) = 0.182) and cancer-specific distress (ηp (2) = 0.056); depression (ηp (2) = 0.621); health-related stigma (ηp (2) = 0.139). In contrast, quality of life declined (ηp (2) = 0.023). The therapeutic relationship; self-management of distress; and relationship support were highly valued aspects of the intervention. Barriers to intervention included avoidance and practical issues. The lung cancer patients who completed the Psychological Wellness intervention reported improvements in psychological outcomes and decreases in stigma in the face of declining quality of life with patients reporting personal benefit from their own perspectives. A randomised controlled trial is warranted to establish the effectiveness of this approach.

Sexuality and exercise in men undergoing androgen deprivation therapy for prostate cancer.

OBJECTIVE: Androgen deprivation therapy (ADT) for the management of prostate cancer results in a range of side effects including sexual dysfunction. Exercise is proposed as a potentially effective therapy to counteract changes in sexual function. The current study explored the impact of ADT on men's sexuality and the effect of exercise on this experience. METHODS: Semi-structured, in-depth interviews were conducted with 18 men (age = 63.1 ± 3.8) who were on ADT for prostate cancer for ≤12 months and who were part of a pre-existing exercise intervention trial. RESULTS: Sexual concerns for men included changes in body image, partner relationships, sex drive, sexual performance and masculinity. In coping with these concerns, men described a sense of personal acceptance of sexual changes through a shift in priorities and values away from penetrative sexual intercourse, knowledge and understanding about ADT, and partner support. Exercise in a group-based setting contributed to the acceptance of sexual changes through affirming strength-based aspects of masculinity and peer support. CONCLUSION: Exercise appears to have utility as a strategy to assist men to manage the negative impact of ADT on sexuality and masculinity more broadly.

A systematic review of psycho-oncology research in Chinese populations: emerging trends.

The burden of cancer in China is increasing with future psycho-oncological interventions crucial. A systematic review of psycho-oncology research in China was undertaken to assess quantity, design and target trends over time. Medline, PsycINFO, CINAHL, ProQuest, Web of Science (1999-November Week 4, 2012) were searched. Inclusion criteria were: included cancer patients and/or partners or caregivers from resident Chinese populations (either at least 80% of participants are from China, Hong Kong or Taiwan); assessed psychological adjustment relating to cancer and published in English after 1 January 1999 and prior to 30 November 2012. In all, 208 articles met inclusion criteria. Of these: 52 were cross-sectional descriptive quantitative; 30 were cross-sectional descriptive qualitative; 27 were prospective descriptive quantitative; 2 were prospective descriptive qualitative; 18 assessed interventions; 79 presented instrument validation. Publications increased eightfold from 1999 to 2012. Most studies included patients (n = 195) with 11 articles focusing on caregivers and two on patient-caregiver dyads. The most common cancer studied was breast cancer. The psycho-oncology research effort in China is dramatically increasing. A focus on culturally relevant approaches to underpin the evaluation of empirically derived interventions is warranted; as is direction of efforts to other cancers such as lung and prostate.

Prevalence and predictors of cancer specific distress in men with a family history of prostate cancer.

OBJECTIVE: To examine prevalence and predictors of cancer-specific distress in undiagnosed men with and without a family history of prostate cancer, and to examine the contribution of perceptions of an affected relative's cancer experience on the distress of unaffected male relatives. METHODS: Men with a first degree relative with prostate cancer (n = 207) and men without a family history (n = 239) from Australia completed a Computer Assisted Telephone Interview. Participants completed the Prostate Cancer Anxiety Subscale of the Memorial Anxiety Scale for Prostate Cancer, measures of perceived risk, and socio-demographic information. Men with a family history provided details about their family history (number of relatives diagnosed with and dead from prostate cancer, relationship to affected relative, months since diagnosis) and reported their perceptions of their affected relative's prostate cancer experience including perceptions of threat related to the relative's diagnosis and perceived treatment phase and prognosis. RESULTS: Cancer-specific distress was low for all men and there was no significant difference in the distress experienced by men with and without a family history. Regression analyses showed that for all men, cancer-specific distress increased with urinary symptoms and decreased in those with higher education and in older participants. For men with a family history, having a relative who died from prostate cancer and perceiving greater threat from a relative's diagnosis was associated with greater cancer-specific distress. CONCLUSIONS: Interventions would benefit from examining appraisals of familial risk and examining prospective assessments of distress in the unaffected male relatives of men with prostate cancer over the course of the cancer trajectory.

Motorcycles and breast cancer: the influence of peer support and challenge on distress and posttraumatic growth.

PURPOSE: Peer support programs based on exercise or challenge activities may have potential to improve well-being for women diagnosed with breast cancer. The current study investigated the role of social comparison and social identity based on group membership on posttraumatic growth (PTG) and distress. METHODS: Fifty-one women diagnosed with breast cancer who participated in a 1,000 mi group motorcycle ride completed pre- and post-ride surveys. Participants had a mean age of 49.82 years (SD = 7.04) and their average time since diagnosis was 6.39 years (SD = 3.89). RESULTS: Cancer-related distress significantly decreased after the ride. PTG did not significantly differ after the ride, which may have been a result of a ceiling effect on this measure. Hierarchical regression analyses showed that pre-ride PTG (p < 0.01) and upward social comparison during the ride (p < 0.05) were related to post-ride PTG. Pre-ride distress was the only variable to remain significantly related to post-ride distress (p < 0.01). CONCLUSIONS: The results of the current study highlight the potential for challenge-based activities to provide a positive peer support environment for women diagnosed with breast cancer. Identifying factors that promote personal growth and reduce cancer-related distress allow us to create a model for the delivery of these challenge-based peer support activities.

Psychological distress and unmet supportive care needs in cancer patients and carers who contact cancer helplines.

Cancer information services are a highly accessible source of support for people affected by cancer. To date the nature and extent of distress experienced by such callers and their unmet support needs have not been well described. A cross-sectional survey of 354 cancer patients and 336 carers who reported elevated distress on contact with a cancer information service assessed socio-demographic variables; anxiety, depression and somatization; unmet supportive care needs; cancer-specific distress; presenting problems; post-traumatic growth. Adjustment to cancer was most commonly reported; followed by anxiety. In all, 53.4% of patients and 45.2% of carers reached caseness in anxiety, depression or somatization. Carers had higher distress ratings and intrusive thinking compared to patients; whereas patients had higher somatization. For patients, most unmet supportive care needs were psychological; for carers unmet needs were related to health care services and information related to the person diagnosed with cancer. Being single, unemployed, in treatment, having higher initial distress scores, higher intrusion and avoidance predicted poorer outcomes. Information service frameworks should include distress screening and clear triage and referral processes for psychological care.

Prohibitin as a novel target protein of luteinizing hormone in ovarian epithelial carcinogenesis.

The exact role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian epithelial carcinoma (OEC) development has not been yet characterized. This prompted us to identify particular proteins to better understand the underlying mechanism. Total proteins from ovarian epithelial tumor (OET) cells treated with gonadotropins were analyzed by proteomics. Western blot and immunohistochemistry were used to validate the target protein (prohibitin) and to detect its expression in human ovarian tissue of serous tumors. As the results, prohibitin was found to be significantly up-regulated by LH, with a maximum of 2.5-fold increase at the concentration of 200 mIU/mL. The expression of prohibitin was steadily decreased from benign serous cystadenomas to borderline tumors and serous carcinomas (P < 0.0001). The difference between any two groups was significant (P < 0.001). Collectively, data from this study indicate that prohibitin is one LH-associated protein and it may be protective of ovarian cancer development and progression, supporting that LH may play an inhibitory role in ovarian tumorigenesis.

When peer support may be most beneficial: the relationship between upward comparison and perceived threat.

OBJECTIVE: Currently, the mechanism by which dyadic peer support programs may facilitate positive psychological adjustment for cancer patients is unclear. This study utilized social comparison theory to examine the effects of peer support on the psychological adjustment of women with breast cancer. METHODS: A cross-sectional survey of 251 recently diagnosed breast cancer patients (52% response), who had received a dyadic peer support intervention, was undertaken assessing anxiety, depression, perceived threat, and upward comparison. RESULTS: Perceived cancer threat significantly moderated the relationship between positive upward comparison and depression levels (p = 0.017). Women who engaged in upward comparisons and who perceived their diagnosis to be more threatening had lower depression levels than women who were less threatened. CONCLUSIONS: Peer support services that provide support from cancer survivors may be especially beneficial for people who appraise their cancer diagnosis as more threatening. The application of theoretical models to future evaluation designs will further increase understanding of the psychological mechanisms involved in the effects of peer support and inform program development.

Predictors of change in unmet supportive care needs in cancer.

OBJECTIVE: Patient Reported Outcome (PRO) assessments can assist health professionals to tailor their health practices to the individual needs of patients and improve patient care over time. The present study assessed prospective predictors of unmet supportive care needs in cancer patients over a six-month period. METHODS: Participants were recruited from a regional cancer treatment centre in Australia and completed the Supportive Care Needs Survey (SCNS) at recruitment (n=439; 61.4% response rate) and six months follow-up (n=396). Hierarchical logistic regression was used to identify predictors of change in unmet needs across each supportive care domain. Predictor variables were socio-demographic, treatment and psychosocial factors including depression, anxiety, social support, and patient satisfaction. RESULTS: Unmet needs were reported by approximately two-thirds of patients at baseline and half of patients at six months follow-up. Having unmet needs at baseline was the strongest predictor of unmet needs at six months. Longer time since diagnosis was a consistent predictor of greater unmet needs, associated with change in physical/daily living, psychological and health system and information unmet needs over time. By contrast, a complex relationship was found in that patient satisfaction, psychosocial and treatment characteristics predicted higher needs in some domains and lower needs in others. CONCLUSIONS: Unmet supportive care needs persist over time and psychological needs may emerge later in the illness continuum. Interventions to meet the needs of longer term cancer survivors are needed and should closely articulate with reported supportive care needs.