The role of diet in cancer: the potential of shaping public policy and clinical outcomes in the UK.

Cancer universally represents one of the largest public health concerns, substantially contributing to global disease burden and mortality. The multifaceted interplay of environmental and genetic factors in the disease aetiology and progression has required comprehensive research to elucidate modifiable elements which can reduce the risk of incidence and improve prognosis. Among these factors, diet and nutrition have emerged as the most fundamental with a significant potential for influence and effect. Nutrition is not only an essential part of human survival, but also a vital determinant of overall health. Certain dietary requirements are necessary to support normal physiology. This includes individualised levels of macronutrients (proteins, carbohydrates and fats) and specific micronutrients (vitamins and minerals). Extensive research has demonstrated that diet plays a role in cancer pathogenesis at the genetic, epigenetic and cellular level. Therefore, its potential as a modifiable determinant of cancer pathogenesis for the purpose of prevention and improving management of disease must be further explored and implemented. The ability to influence cancer incidence and outcomes through dietary changes is underutilised in clinical practice and insufficiently recognised among the general public, healthcare professionals and policy-makers. Dietary changes offer the opportunity for autonomy and control over individuals health outcomes. Research has revealed that particular dietary components, as well as cultural behaviours and epidemiological patterns may act as causative or protective factors in cancer development. This review aims to comprehensively synthesise this research to further explore how to best utilise this knowledge within the community and clinical environment for more effective cancer prevention and therapeutic strategies. The identified key areas for improvement include the development of more specific, widely accepted guidelines, promoting increased involvement of dieticians within cancer multidisciplinary teams, enhancing nutritional education for healthcare professionals and exploring the potential implementation of personalised nutrition tools. A greater understanding of the complex interactions between diet and cancer will facilitate informed clinical interventions and public health policies to reduce global cancer burden and improve care for cancer patients and survivors.

Effect of MYC and PARP Inhibitors in Ovarian Cancer Using an In Vitro Model.

BACKGROUND/AIM: The 8q24 chromosomal region, which contains the MYC and PVT1 candidate oncogenes, is amplified in carcinomas. Both genes have been involved in the etiopathogenesis of ovarian cancer (OC). In this study, we used an in vitro OC model with a known 8q24 copy number increase and in silico tools to investigate the expression of MYC/PVT1 loci and copy number variation in OC. We also assessed the effects of rucaparib (a PARP inhibitor) in the presence or absence of 10058F4 (a MYC inhibitor) on the expression of MYC/linear PVT1/circular PVT1. MATERIALS AND METHODS: Tissue culture, chromosome preparation, RNA extraction, RT-qPCR, FISH, and wound healing assays were employed. OncoDB, cBioportal, UALKAN, and ROC Plotter in silico tools were also utilized. RESULTS: Although PVT1 and MYC expression levels remained unaltered in OC, putative copy number alterations across all cancers showed a marked difference between the two genes, particularly in gain and amplification for MYC. PVT1 expression demonstrated prognostic value for the treatment of patients with serous and endometrioid OC. Both genes correlated with PARP10, FAM83H, and DEPTOR. The use of rucaparib in the presence or absence of the MYC inhibitor (10058F4) in vitro, led to a significant down-regulation in the expression of MYC, linear, and circular PVT1. CONCLUSION: Our data provide a novel insight into the potential interactions of MYC and PVT1 with other genes. Moreover, we identified a new PARP inhibition mechanism down-regulating MYC, as well as the linear and circular PVT1 transcripts. Future work should expand on clinical studies to better understand the prognostic role of PVT1 in OC.

Alterations in Genome Organization in Lymphoma Cell Nuclei due to the Presence of the t(14;18) Translocation.

Chromosomal rearrangements have been shown to alter genome organization, consequently having an impact on gene expression. Studies on certain types of leukemia have shown that gene expression can be exacerbated by the altered nuclear positioning of fusion genes arising from chromosomal translocations. However, studies on lymphoma have been, so far, very limited. The scope of this study was to explore genome organization in lymphoma cells carrying the t(14;18)(q32;q21) rearrangement known to results in over-expression of the BCL2 gene. In order to achieve this aim, we used fluorescence in situ hybridization to carefully map the positioning of whole chromosome territories and individual genes involved in translocation in the lymphoma-derived cell line Pfeiffer. Our data show that, although there is no obvious alteration in the positioning of the whole chromosome territories, the translocated genes may take the nuclear positioning of either of the wild-type genes. Furthermore, the BCL2 gene was looping out in a proportion of nuclei with the t(14;18) translocation but not in control nuclei without the translocation, indicating that chromosome looping may be an essential mechanism for BCL2 expression in lymphoma cells.