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Associations between cancer and Parkinson's disease in U.S. elderly adults.

ABSTRACT: Several studies suggest that cancer is reduced before and after a Parkinson's disease (PD) diagnosis. However, determining relationships among diseases of ageing is challenging due to possible biases in ascertaining disease. This study evaluates the PD and cancer relationship, addressing potential biases.Using Surveillance, Epidemiology, and End Results-Medicare linked data (1992-2005) of adults ? 65 years, we assessed PD risk after cancer comparing PD in 743 779 cancer patients with PD in a non-cancer group (n = 419 432) in prospective cohort analyses. We also conducted a case-control study of 836 947 cancer cases and 142 869 controls to assess cancer following PD. We applied Cox proportional hazards models to estimate hazards ratios (HRs) for PD after cancer and unconditional logistic regression to estimate odds ratios (ORs) for PD preceding cancer, controlling for physician visits and other factors. To explore biases in ascertaining cancer, we examined relationships between cancer and automobile accident injuries, which we expected to be null.No association was observed between cancer and subsequent PD [HR?=?0.97; 95% confidence interval (CI) = 0.92-1.01] nor between cancer and subsequent automobile injuries (HR?=?1.03; 95% CI?=?0.98-1.07). One site, lung cancer, was associated with subsequent reduced PD, which may reflect confounding by smoking. In the case-control analysis, PD was associated with reduced subsequent cancer, overall (OR?=?0.77; 95% CI?=?0.71-0.82) and for several cancer sites. However, the automobile injury/ subsequent cancer association was similar (OR?=?0.83; 95% CI?=?0.78-0.88), suggesting a cancer detection bias after serious health outcomes.In totality, our data do not support a biological relationship between PD and cancer.

SUBMITTER: Freedman DM

PROVIDER: S-EPMC5841885 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

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Associations between cancer and Parkinson's disease in U.S. elderly adults.

Freedman D Michal DM Wu Jincao J Chen Honglei H Engels Eric A EA Enewold Lindsey R LR Freedman Neal D ND Goedert James J JJ Kuncl Ralph W RW Gail Mitchell H MH Pfeiffer Ruth M RM

International journal of epidemiology 20160317 3

<h4>Background</h4>Several studies suggest that cancer is reduced before and after a Parkinson's disease (PD) diagnosis. However, determining relationships among diseases of ageing is challenging due to possible biases in ascertaining disease. This study evaluates the PD and cancer relationship, addressing potential biases.<h4>Methods</h4>Using Surveillance, Epidemiology, and End Results-Medicare linked data (1992-2005) of adults ≥ 65 years, we assessed PD risk after cancer comparing PD in 743 7 ...[more]

PMID: 26989123

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Project description:Alzheimer's (AD) and Parkinson's diseases (PD) are the two most prevalent neurodegenerative disorders in human populations. Epidemiological studies have shown that patients suffering from either condition present a reduced overall risk of cancer than controls (i.e., inverse comorbidity), suggesting that neurodegeneration provides a protective effect against cancer. Reduced risks of several site-specific tumors, including colorectal, lung, and prostate cancers, have also been observed in AD and PD. By contrast, an increased risk of melanoma has been described in PD patients (i.e., direct comorbidity). Therefore, a fundamental question to address is whether these associations are due to shared genetic and molecular factors or are explained by other phenomena, such as flaws in epidemiological studies, exposure to shared risk factors, or the effect of medications. To this end, we first evaluated the transcriptomes of AD and PD post-mortem brain tissues derived from the hippocampus and the substantia nigra and analyzed their similarities to those of a large panel of 22 site-specific cancers, which were obtained through differential gene expression meta-analyses of array-based studies available in public repositories. Genes and pathways that were deregulated in both disorders in each analyzed pair were examined. Second, we assessed potential genetic links between AD, PD, and the selected cancers by establishing interactome-based overlaps of genes previously linked to each disorder. Then, their genetic correlations were computed using cross-trait LD score regression and GWAS summary statistics data. Finally, the potential role of medications in the reported comorbidities was assessed by comparing disease-specific differential gene expression profiles to an extensive collection of differential gene expression signatures generated by exposing cell lines to drugs indicated for AD, PD, and cancer treatment (LINCS L1000). We identified significant inverse associations of transcriptomic deregulation between AD hippocampal tissues and breast, lung, liver, and prostate cancers, and between PD substantia nigra tissues and breast, lung, and prostate cancers. Moreover, significant direct (same direction) associations of deregulation were observed between AD and PD and brain and thyroid cancers, as well as between PD and kidney cancer. Several biological processes, including the immune system, oxidative phosphorylation, PI3K/AKT/mTOR signaling, and the cell cycle, were found to be deregulated in both cancer and neurodegenerative disorders. Significant genetic correlations were found between PD and melanoma and prostate cancers. Several drugs indicated for the treatment of neurodegenerative disorders and cancer, such as galantamine, selegiline, exemestane, and estradiol, were identified as potential modulators of the comorbidities observed between neurodegeneration and cancer.

Dataset Information

Associations between cancer and Parkinson's disease in U.S. elderly adults.

Publications

Associations between cancer and Parkinson's disease in U.S. elderly adults.

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