Parkinson's Disease and Cancer: A Register-based Family Study

Abstract

We wanted to compare cancer incidence rates between Parkinson's disease (PD) patients and persons without PD, as well as between siblings of these groups. We conducted a family-based matched cohort study based on nationwide Swedish health registries and the Swedish Multi-Generation Register. We assessed risk of incident cancer in PD patients (n = 11,786) during 1964-2009 versus a matched cohort of PD-free individuals (n = 58,930) and in siblings of PD patients (n = 16,841) versus siblings of PD-free individuals (n = 84,205). Hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards regression. Cancer occurrence was slightly higher in PD patients than in PD-free individuals (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 1.00, 1.10), largely because of cancers arising within 1 year before or after the index date for PD, but risk of smoking-related cancers was lower (HR = 0.87, 95% CI: 0.79, 0.96). PD patients had a higher risk of melanoma both up to 1 year before the PD index date (HR = 1.53, 95% CI: 1.23, 1.91) and from 1 year after the index date onward (HR = 1.46, 95% CI: 1.01, 2.10). In the sibling comparison, cancer occurrence was largely similar. These results indicate that melanoma risk is higher among PD patients and that mechanisms other than familial ones explain the association.

Parkinson’s Disease, Melanoma, and Keratinocyte Carcinoma: A Population-Based Study

“…A Danish cohort study of 14,088 PD patients [16] and a case-control study of 8,090 Danish PD cases [17] also reported a positive association with ORs of 1.25 and 1.26, respectively. A positive relationship between PD and subsequent NMSCs was also reported in later studies [7, 18, 19], with point estimates ranging between 1.29 and 1.81 [1]. …”

Cancers Preceding Parkinson’s Disease after Adjustment for Bias in a Danish Population-Based Case-Control Study

“…Thus, our estimates are less likely to be affected by outcome misclassification and potential (negative) confounding by smoking than the previous study. In our study, we observed positive association for malignant melanoma, which was in line with previous studies [6,8,12]. Positive associations have been reported in previous Danish registrybased studies for breast cancer [32,33], opposite to what we saw in our study.…”

“…Since then, further evidence accumulated from case series [2][3][4] and epidemiological studies [5][6][7][8][9][10][11][12] that cancer is rarer among PD patients compared with the general population except for melanoma and perhaps breast cancer. Cancer and PD have been attributed to distinct and opposing biological mechanisms with the former being characterized by uncontrolled cell proliferation, and the latter by abnormal neuronal cell loss that occurs progressively [13].…”

“…On the other hand, registry-based studies [8,12,28] with a relatively large number of PD cases while investigating specific cancers lacked information on individual-level lifestyle factors, such as smoking and physical activity that may confound cancer-PD associations. We conducted a population-based case-control study of PD in Denmark (PASIDA) that was much larger than previous interview-based studies and collected detailed information on lifestyle factors.…”

Treatment with diphenyl–pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death

“…However, two subsequent studies (9,10) showed that the PD susceptibility loci and PDspecific single nucleotide polymorphisms, identified in genomewide association studies, neither play a role in melanoma development nor contribute to the association between PD and melanoma. Likewise, a family-based matched cohort study, conducted in Sweden, ruled out familial genetic factors as the reason for the association between PD and melanoma (11).…”