Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies

SIMPLE SUMMARY: Cancer escape links to the insufficient immune response. Thus, transition from a pre-cancerous state to cancerous development induced by morbidities competing for the immune resources is possible. We propose a simple but general conceptual model which suggests a unified explanation of cancer escape and other clinical and epidemiological observations, such as age-dependent prevalence and increased risk of getting cancer for patients with chronic inflammatory diseases. Myeloproliferative malignancy is used as a case throughout when specific data is considered but we conjecture the finding are general since they originate from immune deficiencies. ABSTRACT: (1) Background: We consider dormant, pre-cancerous states prevented from developing into cancer by the immune system. Inflammatory morbidity may compromise the immune system and cause the pre-cancer to escape into an actual cancerous development. The immune deficiency described is general, but the results may vary across specific cancers due to different variances (2) Methods: We formulate a general conceptual model to perform rigorous in silico consequence analysis. Relevant existing data for myeloproliferative malignancies from the literature are used to calibrate the in silico computations. (3) Results and conclusions: The hypothesis suggests a common physiological origin for many clinical and epidemiological observations in relation to cancers in general. Examples are the observed age-dependent prevalence for hematopoietic cancers, a general mechanism-based explanation for why the risk of cancer increases with age, and how somatic mutations in general, and specifically seen in screenings of citizens, sometimes are non-increased or even decrease when followed over time. The conceptual model is used to characterize different groups of citizens and patients, describing different treatment responses and development scenarios.