Parkinson's disease and cancer: a systematic review and meta-analysis of over 17 million participants.

Objective: To systematically review and qualitatively evaluate epidemiological evidence on associations between Parkinson's disease (PD) and cancer via meta-analysis.

Data Sources: MEDLINE via PubMed, Web of Science and EMBASE, until March 2021.

Study Selection: Included were publications that (1) were original epidemiological studies on PD and cancer; (2) reported risk estimates; (3) were in English. Exclusion criteria included: (1) review/comments; (2) biological studies; (3) case report/autopsy studies; (4) irrelevant exposure/outcome; (5) treated cases; (6) no measure of risk estimates; (7) no confidence intervals/exact p values and (8) duplicates.

Data Extraction And Synthesis: PRISMA and MOOSE guidelines were followed in data extraction. Two-step screening was performed by two authors blinded to each other. A random-effects model was used to calculate pooled relative risk (RR).

Main Outcomes And Measures: We included publications that assessed the risk of PD in individuals with vs without cancer and the risk of cancer in individuals with vs without PD.

Results: A total of 63 studies and 17 994 584 participants were included. Meta-analysis generated a pooled RR of 0.82 (n=33; 95% CI 0.76 to 0.88; p<0.001) for association between PD and total cancer, 0.76 (n=21; 95% CI 0.67 to 0.85; p<0.001) for PD and smoking-related cancer and 0.92 (n=19; 95% CI 0.84 to 0.99; p=0.03) for non-smoking-related cancer. PD was associated with an increased risk of melanoma (n=29; pooled RR=1.75; 95% CI 1.43 to 2.14; p<0.001) but not for other skin cancers (n=17; pooled RR=0.90; 95% CI 0.60 to 1.34; p=0.60).

Conclusions: PD and total cancer were inversely associated. This inverse association persisted for both smoking-related and non-smoking-related cancers. PD was positively associated with melanoma. These results provide evidence for further investigations for possible mechanistic associations between PD and cancer.

Prospero Registration Number: CRD42020162103.