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The published validation study of a new in vitro mammalian test, GreenScreen HC, has shown it to be both highly specific and highly sensitive in the detection of genotoxic carcinogenicity, with values higher than those for many of the regulatory genotoxicity tests. This test has great potential to fill a need for a new pre-regulatory test that is easier, cheaper and quicker to perform, while still being predictive of rodent carcinogenicity. In this thesis experimentation fell into three groups - investigation of compounds with positive results in one or more regulatory mammalian in vivo tests; testing of compounds with little or contradictory regulatory genotoxicity data and investigation into the effect of the GADD45a regulatory elements included within the reporter plasmid. The testing of false positive compounds showed GreenScreen HC to be second only to the MNT test for specificity and confirmed previously published data stating the high levels of specificity of GreenScreen HC. Testing of groups of compounds with little genotoxicity data highlighted genotoxic potential for a number of compounds including a number of the histone deacetylase inhibitors and the synthetic retinoid CD437. The effect of the regulatory elements included in the assay were investigated through use of reporters with mutated response elements. With each mutation, the induction of GADD45a was lessened and this highlighted the importance of the use of cells with fully component DNA damage response pathways for genotoxicity testing.

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Evaluating the burden of cancer on society is of great interest to health officials and planning authorities. It is of particular importance to be able to correctly estimate the burden of cancer in the coming years in order that appropriate provisions can be put in place. The vast majority of developed, and also developing, countries have a cancer registry set-up and have at least 20 years of complete data. In the leading developed countries, the cancer registry data is complete and reliable for the past 50 years. Using this data it is possible to estimate key quantities that can be used to assess the burden of cancer. Prevalence gives a good proxy for the burden of cancer on society; it gives an estimate of the number of people who are alive having had a previous cancer diagnosis. Prevalence can be estimated by combining models for incidence and patient survival. To accurately model the prevalence, it is important to develop the best methods for modelling the incidence and patient survival from population-based cancer registries. Therefore, as part of this thesis, novel methods have been developed for projecting cancer incidence into the future using an approach that treats the data continuously. Also, methods for projecting cancer patient survival have been assessed and improved as part of the work by effectively estimating the quantities in continuous time. These projected estimates have been combined to give future estimates of cancer prevalence. Making predictions is obviously fraught with danger and, therefore, it should be made clear that these projections are liable to be uncertain and based on strong assumptions. However, if the assumptions of these models are fully understood, they may well provide a useful tool for health and financial planning in terms of assessing the disease burden due to the differing forms of cancer.

Aim: To explore how British South Asian (BSA) and British White (BW) cancer patients coped during the nine months following referral to a UK Cancer Centre. Material and methods: This quantitative cross sectional study compared symptoms of anxiety and depression between 94 BSA and 185 BW patients at baseline, at three and nine months. Associations between mood and coping strategies and selected environmental factors (symptom burden, cancer beliefs and the therapeutic relationship) were analysed. Questionnaires, available in English, Gujarati and Hindi, were the Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire (PHQ-9), Emotion Thermometers (inclusive of the Distress Thermometer and Problem Checklist), Cancer Insight and Denial Questionnaire (CIDQ), Mini MAC, Brief Illness Perception Questionnaire (BIPQ), Physician/Patient Trust and Cancer Beliefs. Results: BSA patients reported higher rates of depressive symptoms compared to BW patients longitudinally e.g. (HADS D≥8: baseline: BSA 35.1% v BW 16.8% p=0.001; 3 months BSA 45.6% v BW 20.8% p=0.001; 9 months BSA 40.6% v BW 15.3% p=0.004). A similar ethnic gulf was detected in rates of anxiety until 3 months (HADS ≥8 at baseline (BSA 54.3% v BW 36.2% p=0.006; 3 months BSA 47.4% v BW 32.6%; 9 months BSA 40.6% v BW 28.2% p=0.25). BSAs used potentially maladaptive coping strategies more frequently at baseline, e.g. hopelessness/helplessness (p=0.005), fatalism (p=0.0005), avoidance (p=0.005). The symptom burden was greater on BSA patients. This was reflected in an ethnic difference in depressive symptoms. Some cancer beliefs and preferences for the therapeutic relationship influenced how patients coped. Conclusion: Health professionals need to be aware of the greater probability of psychological distress occurring among BSA cancer patients and how this may present clinically if this ethnic disparity in mental wellbeing is to be addressed. Clinicians need to establish the cultural context in which an individual experiences cancer.

This dissertation aims to explore whether linguistic or cultural factors affected responses to the EORTC QLQ-C30 cancer quality of life instrument. Questionnaire data from 125 separate studies and representing over 39,000 respondents from 49 countries were received and recoded into a standard format. Differential item functioning (DIF) analyses using ordinal logistic regression were conducted in order to determine whether there were different response patterns to each item of the EORTC QLQ-C30 according to (1) the translation used, and 92) the geographic/cultural grouping, after controlling for the overall level of quality of life in that domain. Although most response patterns were similar, statistically significant DIF was identified in at least one item for nearly all translations and geographic groupings examined. interviews with bilingual people were used to help decide whether the DIF was due to the translation or to cultural factors, or whether this was caused by DIF in another item in the same scale (pseudo-DIF). Overall, the results suggest that most of the DIF was caused by translation issues, but there was a suggestion of cultural response patterns for East Asian versus Western countries. A literature review of differential item functioning (DIF) methods found a large number of available methodologies, which are described in this thesis, but no clear consensus as to the recommended method. Computer simulations were used to examine the performance of the ordinal logistic regression DIF methodology when the scale had a small number of items. Separate scale-level regression analyse were also conducted to determine whether there were cultural differences in the emphasis placed on each aspect of quality of life.

Health care professionals are increasingly aware of the impact of cancer and cancer treatment on sexuality and intimacy, which are important components of quality of life until death. However, professionals are struggling with addressing these issues with cancer patients and their partners (clients). One of the reasons is lack of in-depth knowledge of clients’ experiences. Aims of the study To increase understanding of how cancer and cancer treatment impact upon the experience of sexuality and intimacy of patients and their partners To increase understanding of how cancer patients and their partners experience the way health care professionals address sexuality and intimacy To gain insight into health care professional’s perceptions of their role regarding sexuality and intimacy for cancer patients and their partners To develop patient driven models, tools and recommendations to acknowledge sexuality and intimacy in cancer and palliative care Methodology Using a hermeneutic phenomenological approach, data were collected in the Netherlands through interviewing 8 patients, 7 couples and 6 partners of patients affected by cancer, and 20 health care professionals working in cancer and palliative care. Analysis was based on the hermeneutic circle, moving from the whole to the parts and back, and was enhanced by the use of ATLAS.ti, by peer debriefing and by expert consultation. Findings Findings are based on multiple perspectives and are presented in a storyline using vignettes. The core theme of the findings is ‘worlds apart’, manifesting itself on several levels: between clients and professionals, between partners and on the intra-psychic level of the patient. Cancer and cancer treatment impact on sexual function, sexual relationship and sexual identity, resulting in a unique outcome for every client or couple. Most participants reported that health care professionals did not address sexuality and intimacy, and attempts made often did not match participants’ preferences. Most participants said they would value discussing the impact of cancer on their sexuality and intimacy. This does require a ‘personalized’ approach from the health care professional from the start of the interaction with the patient onwards. Based on the findings of this study and the available literature, a systemic client driven model (the BLISSS communication model) and an integral team approach (model of stepped skills) were developed. Conclusions and recommendations All types of cancer and cancer treatment potentially have an enormous adverse and enduring impact on sexuality and intimacy. Therefore, sexuality and intimacy should be put on the agenda of health care education and of every cancer and palliative care team. Both personal factors and lack of guidance hinder professionals in addressing sexuality and intimacy. Using the stepped skills team approach, team members can develop clear and complementing roles in order to properly address sexuality and intimacy issues, resulting in adequate support for clients in all sexual domains: sexual functioning, sexual relationship and sexual identity. Team members should be trained to develop the competencies matching their role.

Socioeconomic disparities in health have been demonstrated over a wide range of health outcomes. A differential capacity to cope with stressful life events has been proposed as one mechanism contributing to disparities. SES differences in coping with cancer-related stressors are the subject of this thesis. Study 1 examined SES differences in psychological distress associated with cancer screening. Lower SES groups had lower psychosocial wellbeing but were not more vulnerable to adverse psychological consequences. Study 2 tested the hypothesis that SES differences in adjustment to a cancer diagnosis are greater when the prognosis is poorer. There was some evidence that lower SES groups were more adversely affected by a more advanced disease stage diagnosis compared to higher SES groups. The qualitative interviews in Study 3 considered the possibility that this was due to differential experience of care, but found little evidence that cancer patients' experiences of medical care differed by SES. Studies 4, 5 and 6 used a large longitudinal sample of cancer patients (breast, prostate and colorectal). Study 4 explored whether SES moderated psychosocial adjustment related to the types of treatment received, presence of co-morbidity or disease stage at diagnosis. The effect of receiving surgery appeared to diminish rather than increase SES differences in adjustment. Study 5 showed that higher SES groups had more psychosocial resources to cope with a cancer diagnosis and that resources were related to psychosocial wellbeing, but despite this, Study 6 found no evidence that lower SES groups experienced poorer adjustment to a cancer diagnosis over time. Overall the studies found little evidence that lower SES gives greater vulnerability to serious stressors, and if anything, suggested that a cancer diagnosis seemed to minimise the expected SES differences in psychological wellbeing.

The diagnosis of childhood cancer is recognised as a significant stressor for families. There is a growing body of research exploring the experiences of parents and healthy siblings during the treatment of childhood cancer. The first paper is a systematic review of 28 qualitative studies that explored the experiences of mothers and fathers from different countries and cultures. Key findings included the desire to feel in control, the need to continuously adjust, various coping styles were adopted, emotional and practical support was valued, and gender and cultural differences were reported. Clinical implications include the need to provide clear information and aid the sense of control, care needs to be individualised, and fathers' needs should be acknowledged and met. The second paper aimed to address some of the gaps in the literature on healthy siblings, as few studies have explored the experiences of adolescent healthy siblings. A qualitative study was carried out using grounded theory to explore adolescent healthy siblings' experiences across the duration of treatment for childhood cancer. A semi-structured retrospective interview was completed with eight participants. A grounded theory model was developed, which illustrates how the healthy siblings' experience changed over time, with the most challenging period being the diagnosis and initial phase of treatment. Their experiences appeared to depend on a number of factors including: how they managed the stressors; temperament; family relationships; individual coping strategies; and support received. Developmental changes associated with adolescence appeared to further serve as a potential protective factor. Clinical implications include health care professionals needing to ensure healthy siblings have appropriate support in place and the required coping skills to reduce the chance of psychosocial problems developing. There is a particular need for early support, as healthy siblings are likely to particularly struggle between the diagnosis and initial treatment.

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