Comorbid Cancer in Parkinson's Disease
Department of Health Research and Policy, Stanford University, Stanford, California 94305-5405, USA. Movement Disorders
(Impact Factor: 5.68).
09/2010; 25(12):1809-17. DOI: 10.1002/mds.23246
The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age- and sex-matched control subjects identified during two periods (1994-1995 and 2000-2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD-cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD-cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non-PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54-1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70-1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40-5.2; after PD, RR = 1.6; 95% CI 0.71-3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking.
Available from: PubMed Central
- "Several large epidemiological studies have demonstrated that both Alzheimer's disease – and Parkinson's disease – have negative associations with cancer. On the other hand, some individual tumours may confer an increased risk of Parkinson's disease , . Mechanisms proposed to explain these findings include common pathways of cell cycle protein dysregulation , , mitochondrial dysfunction , and aberrant oxygen sensing . "
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ABSTRACT: Cancer appears to be inversely associated with both Alzheimer's and Parkinson's disease. The relationship between cancer and sporadic motor neuron disease (SMND), however, remains uncertain. Most previous cancer-SMND studies have been undertaken in northern hemisphere populations. We therefore undertook a case-control study to see if a link between cancer and SMND exists in an Australian population. A questionnaire was used to compare past cancer diagnoses in 739 SMND patients and 622 controls, recruited across Australia. Odds ratios with 95% confidence intervals were calculated to look for associations between cancer and SMND. A history of cancer was not associated either positively or negatively with a risk of subsequent SMND. This result remained when age, gender, smoking status, and the four SMND diagnostic subgroups were taken into account. No association was observed between SMND and specific tumours, including melanoma, a common malignancy in Australia. In conclusion, this Australian case-control study does not support an association between a past history of cancer and the development of SMND. This suggests that some pathogenetic mechanisms, such as apoptosis, are less relevant in SMND than in other neurodegenerative diseases where negative associations with cancer have been found.
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ABSTRACT: Epidemiological studies have consistently shown that individuals with Parkinson's disease (PD) are less likely to develop nonmelanoma cancers and vice versa. In contrast, the co-occurrence of PD and melanoma has been reported in numerous studies. The exact mechanisms underlying the observed cancer-PD association are not clear. Different hypotheses have been put forward, including shared environmental/lifestyle factors (e.g., smoking and socioeconomic status) and common genetic components (e.g., parkinson protein 2 [PARK2], leucine-rich repeat kinase 2 [LRRK2], Parkinson disease [autosomal recessive, early onset] 7 [PARK7, DJ-1] and pigmentation genes). In the current review, we summarize recent findings to offer new insight into the pathogenesis of both conditions.
Available from: Joseph Jankovic
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ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of melanin-positive, dopaminergic neurons in the substantia nigra. Although there is convincing epidemiologic evidence of a negative association between PD and most cancers, a notable exception to this is that melanoma, a malignant tumor of melanin-producing cells in skin, occurs with higher-than-expected frequency among subjects with PD and that melanoma patients are more likely to have PD. A clear biological explanation for this epidemiological observation is lacking. Here, we present a comprehensive review of published literature exploring the association between PD and melanoma. On the basis of published findings, we conclude that (i) changes in pigmentation including melanin synthesis and/or melanin synthesis enzymes, such as tyrosinase and tyrosine hydroxylase, play important roles in altered vulnerability for both PD and melanoma; (ii) changes of PD-related genes such as Parkin, LRRK2 and α-synuclein may increase the risk of melanoma; (iii) changes in some low-penetrance genes such as cytochrome p450 debrisoquine hydroxylase locus, glutathione S-transferase M1 and vitamin D receptor could increase the risk for both PD and melanoma and (iv) impaired autophagy in both PD and melanoma could also explain the association between PD and melanoma. Future studies are required to address whether altered pigmentation, PD- or melanoma-related gene changes and/or changes in autophagy function induce oncogenesis or apoptosis. From a clinical point of view, early diagnosis of melanoma in PD patients is critical and can be enhanced by periodic dermatological surveillance, including skin biopsies.
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