Abstract
Objective: To evaluate the extent to which cancer, a biological opposite to neurodegenerative disorders, may affect the onset and progression of Parkinson's disease (PD).Methods: A nested case-control design in consecutive PD patients with (cases) vs. without (controls) cancer was used to compare time to clinical diagnosis and time to Hoehn & Yahr (H&Y) staging score ≥ 3 as a measure of progression. Further, we compared PD onset and progression between cases with cancer diagnosis before (cancer before PD group) and after (cancer after PD group) PD onset. Independent variables were age at PD onset, motor subscale of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, sex, cognitive impairment, falls, depression, anxiety, dementia, and autonomic symptoms. Time to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR). Group differences were evaluated using unpaired t-test or Fisher's exact test.Results: The clinical PD onset was later in cases vs. controls (median 67.2 vs. 59.8 years; p < 0.001), but the adjusted time to H&Y ≥ 3 was similar between groups (HR = 0.67; p = 0.13). Skin cancers constituted 75% of all cancers in cases. Amongst skin cancers, compared to controls, cases had an older age at PD onset (67.8 vs. 59.8 years; p < 0.001). There was no difference in risk of progression in PD patients with skin cancer compared to controls (HR = 0.54, p = 0.09).Conclusions: Cancer, in particular of the skin, may delay the onset but not the progression of PD. Future prospective observational studies are warranted to elucidate the complex interactions between these biologically divergent disorders.
Highlights
The relationship between cancer and sporadic Parkinson’s disease (PD) has recently come under scrutiny based on common epidemiological and genetic (e.g., CYP2D6 alleles) factors, which suggest convergent mechanisms.While sporadic PD has been associated with a lower incidence of global cancers, skin cancers, prostate, and breast cancers have been reported with higher prevalence in PD compared to age-matched controls [1, 2].A Hoehn and Yahr staging score of ≥3 is defined by the presence of postural instability, a major motor-based disability milestone in PD [3,4,5]
During a median follow up of 7 years, 78 (31%) reached H&Y score ≥ 3, at a median time of 16 years
There was no difference in risk of progression in PD patients with skin cancer compared to controls (HR = 0.54, p = 0.09)
Summary
The relationship between cancer and sporadic Parkinson’s disease (PD) has recently come under scrutiny based on common epidemiological (e.g., smoking, pesticide, estrogen exposure) and genetic (e.g., CYP2D6 alleles) factors, which suggest convergent mechanisms.While sporadic PD has been associated with a lower incidence of global cancers, skin cancers (both melanoma and nonmelanoma skin cancers), prostate, and breast cancers have been reported with higher prevalence in PD compared to age-matched controls [1, 2].A Hoehn and Yahr staging score of ≥3 is defined by the presence of postural instability, a major motor-based disability milestone in PD [3,4,5]. The relationship between cancer and sporadic Parkinson’s disease (PD) has recently come under scrutiny based on common epidemiological (e.g., smoking, pesticide, estrogen exposure) and genetic (e.g., CYP2D6 alleles) factors, which suggest convergent mechanisms. While sporadic PD has been associated with a lower incidence of global cancers, skin cancers (both melanoma and nonmelanoma skin cancers), prostate, and breast cancers have been reported with higher prevalence in PD compared to age-matched controls [1, 2]. Using the time to this milestone as a surrogate of progression, we sought to evaluate the effect of cancers, as disorders characterized by dysregulated cellular proliferation, on the time to symptom onset and to H&Y ≥ 3 in PD, a disorder of dysregulated cellular degeneration
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