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

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.

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