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Epidemiological and molecular associations between central nervous system disorders and cancer

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Epidemiological and molecular associations between central nervous system disorders and cancer

dc.contributor.advisor	Tabarés Seisdedos, Rafael
dc.contributor.advisor	Catalá López, Ferrán
dc.contributor.advisor	Climent Bataller, Joan
dc.contributor.author	Forés Martos, Jaume
dc.contributor.other	Departament de Bioquímica i Biologia Molecular	es_ES
dc.date.accessioned	2021-06-29T11:41:49Z
dc.date.available	2021-06-30T04:45:05Z
dc.date.issued	2021	es_ES
dc.date.submitted	21/06/2021	es_ES
dc.identifier.uri	https://hdl.handle.net/10550/79838
dc.description.abstract	The study of comorbidity is becoming a key topic in biomedical research, which is especially relevant in the context of population ageing. Comorbidity has profound implications for individuals, practitioners, and health care systems. As a consequence, increasing efforts are being made by the scientific community to characterize better how disorders relate to each other and to identify the factors producing these associations. Cancer and central nervous system (CNS) disorders are among the top leading causes of death and disease burden worldwide. In recent decades direct and inverse patterns of association between CNS disorders and cancer have been reported. However, observational studies have often found contrasting results. Consequently, evidence synthesis methods such as systematic reviews and meta-analysis have emerged as a critical tool to synthesize and evaluate the quality of the evidence regarding a specific research question. In addition, in the course of the Omics era, an unprecedented amount of information regarding the molecular bases of individual disorders has been produced, opening the door to the study of comorbidity from a molecular perspective through the identification of joint alterations in variants, genes, and biological processes. In the present thesis, we aimed to characterize the epidemiological and molecular associations between CNS disorders and cancer and to identify the potential role of their indicated medications. To this end, we first determined if CNS disorder patients presented an altered risk of subsequent cancer incidence and mortality by conducting systematic reviews and meta-analyses of observational studies. Second, we investigated if CNS disorders and cancers presented joint patterns of transcriptomic dysregulation using differential gene expression meta-analysis and weighed co-expression network analysis methods. Third, interactome-based methods and genetic correlations were employed to study the involvement of disease-associated genes and shared genetic variability. Finally, the impact of the medications indicated for the treatment of both sets of disorders in the reported comorbidities was assessed by the analysis of a large repository including information of cell lines treated with the indicated drugs. Our results suggest that patients suffering from neurodegenerative disorders are at a reduced risk of subsequent cancer incidence and mortality compared to controls. Autism spectrum disorder, bipolar disorder, and schizophrenia (SCZ) patients are at an increased risk of cancer mortality but not cancer incidence, whereas major depression patients presented an increased risk of cancer incidence and mortality. Several associations between CNS disorders and site-specific cancers were also identified. Significant direct and inverse patterns of transcriptomic dysregulation between CNS disorders and cancers were observed in our transcriptomic analyses, as well as the presence of joint alterations in several biological processes (i.e., cell cycle, apoptosis, immune system, and oxidative phosphorylation). Significant genetic correlations were also identified between CNS disorders and cancers, including those observed between Parkinson’s disease and melanoma and SCZ and breast cancer. Finally, several drugs indicated for the treatment of CNS disorders, such as antipsychotics, antidepressants, and acetyl-cholinesterase inhibitors were found to produce transcriptomic alterations that mimicked or reversed those found in some cancer types, indicating their potential role in the CNS and cancer comorbidity.	es_ES
dc.format.extent	291 p.	es_ES
dc.language.iso	en	es_ES
dc.subject	comorbidity	es_ES
dc.subject	central nervous system disorders	es_ES
dc.subject	cancer	es_ES
dc.subject	systematic reviews	es_ES
dc.subject	meta-analysis	es_ES
dc.subject	transcriptomics	es_ES
dc.subject	interactome	es_ES
dc.subject	genetic correlations	es_ES
dc.subject	medications	es_ES
dc.title	Epidemiological and molecular associations between central nervous system disorders and cancer	es_ES
dc.type	doctoral thesis	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS ::Epidemiología	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS ::Psiquiatría	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS ::Patología::Oncología	es_ES
dc.subject.unesco	UNESCO::QUÍMICA::Bioquímica ::Biología molecular	es_ES
dc.embargo.terms	0 days	es_ES