Inverse and Direct Cancer Comorbidity in People with Central Nervous System Disorders: A Meta-Analysis of Cancer Incidence in 577,013 Participants of 50 Observational Studies

Abstract

Background: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ). Method: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively. Results: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I² = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I² = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I² = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I² = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I² = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I² = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I² = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I² = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I² = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ). Conclusion: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.

Mood and Anxiety Disorders as Early Manifestations of Medical Illness: A Systematic Review

“…In a study [110], about 50% of psychiatric patients who suffered from medical conditions remained undiagnosed as to the underlying physical disorders; primary care physicians failed to diagnose the physical illness in 32% of cases and psychiatrists in 48%, even though having a psychiatric disorder may be associated with an increased risk of medical illness (e.g. breast cancer) [111]. Primary care physicians may not pursue a medical workup of cases that appear to be overtly psychiatric in nature; similarly, patients having had previous psychiatric treatment may prejudice the clinical judgment of the physician [112].…”

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

“…In interpreting our findings, several factors, particularly epidemiology of melanoma, natalizumab‐associated progressive multifocal leukoencephalopathy (PML), various aspects of the TOUCH Risk Management (RiskMAP) Action Plan, and the Safety Surveillance Program in this RiskMAP (Table 3), potential pathophysiology, and an overview of pharmacovigilance efforts for opportunistic complications of medications, should be considered 6, 7, 8, 9, 10, 11, 13, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47.…”

“…Multiple studies evaluated incidence of melanoma among MS patients, although none reported convincing epidemiologic or biologic associations or relative risk estimates 26, 27, 28, 37. Capkun et al.…”

“…noted a slight decrease in melanoma rate among MS patients from a large sample, but do not report on melanoma risks among natalizumab‐treated MS patients 37. Another study reviewing incidence of cancer in MS (sampling 54,929 patients) concluded that melanoma rates were lower for people with MS compared to melanoma among the general population 26. One study reported on 74 patients with MS treated with natalizumab 38.…”

The minus of a plus is a minus. Mass death of selected neuron populations in sporadic late-onset neurodegenerative disease may be due to a combination of subtly decreased capacity to repair oxidative DNA damage and increased propensity for damage-related apoptosis

“…Later, the existence of inverse comorbidity with cancer was confirmed for PD and HD. [99,100] It is possible that common mechanism/s may be involved in the pathogenesis of LONDD and cancer. These mechanisms are probably subject to modulation by other genetic and/or environmental factors so that the potential outcomes would rarely coincide in the same patient.…”