Ethnicity: Does Ethnicity Play A Role In The Relationship Between Parkinsons And Cancer
A study, conducted in 2015 in Taiwan among people of Chinese heritage, indicated an increased risk of cancer in people with PD. In order to explain why this study did not conform to prior results, the researchers suggested that the relationship between cancer and PD may differ in different ethnic populations. Particular genes influence cancer risk as well as PD risk, so it should come as no surprise that these factors may change in different populations. However, much more work must be done to confirm this result, and currently there are no changes to cancer screening for PD patients of particular ethnicities.
Microglia: A Key Player
The brain is a common metastatic site for various types of cancers, especially lung cancer, which suggests failure of the immune defense in the brain environment. Microglia are believed to be the most important immune cells in the CNS. Interestingly, significant microglial activation has been observed in the vicinity of glioma tumor cells . In contrast to CNS inflammation, microglia associated with brain tumors do not seem to be active in inducing an effective antitumor response. The exact mechanism of this microglial inactivation remains unclear. There is evidence that some cytokines, such as IL-10 released from activated microglia, play important roles in local immunosuppression and progression of glioma, particularly promoting proliferation of tumor cells and their infiltration into surrounding normal brain tissue . Microglia also play an important role in phagocytosing tumor cells. During the past decades, more attention has been paid to the secretory property and chemotaxis of microglia, but microglial phagocytosis is not well-studied. The activity of phagocytosis can be modulated by cancer cells or the cancer environment. However, whether microglial phagocytosis functions to contribute to cancer or cancer defense still needs further investigation. A better understanding of microglia function is important for the development of immune-based treatment strategies against malignant brain tumors.
Parkinsons Disease And Melanoma
Even in studies that have established a lower overall cancer risk in people with PD, the risk of certain specific types of cancers is higher than in the general population.
Melanoma is a type of skin cancer that has been consistently linked to PD. People who have had melanoma are at an increased risk for PD and people who have PD are at an increased risk of melanoma. The relationship between melanoma and PD is intriguing:
- The substantia nigra, or the black substance, is the area of the brain that contains the dopaminergic neurons that degenerate in PD. These neurons are full of neuromelanin, a dark pigment found in the brain which is related to melanin, a dark pigment found in the skin.
- Levodopa is a precursor for melanin and neuromelanin.
If a person regularly ingests Levodopa, he/she may be fueling the production of melanin, and possibly the production of melanin-containing cells, which in theory would increase the likelihood of melanoma. However, some studies have demonstrated that the increased melanoma risk is present in patients with PD even before Levodopa is started, suggesting that the relationship is not due to Levodopa intake but rather to a genetic link.
Epidemiological studies have shown an increased risk of non-melanoma skin cancers in PD patients as well.
What to do if you have an increased melanoma risk?
You should know what other melanoma risk factors you have. These include:
These tips below are applicable to all adults with and without PD:
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Tumor Suppressor Gene P53
The tumor suppressor gene p53 has been shown to play a role in human neurodegenerative disorders like PD. Therefore, chemical inhibitors of p53 may be effective in suppressing the neurodegenerative process in PD . Loss of p53 function occurs in many human tumors including melanoma . Therefore, it is possible that there may be reduced risk for PD in melanoma patients who harbor the inactivating p53 mutations. Factors like p53 that promote one disorder while protecting against the other may explain the fact that comorbidity between PD and melanoma is imperfect .
Whos At A High Risk Of Osteoporosis
- People living with Parkinsons
- Those with low body weight
- Those with a family history of osteoporosis
- Those with a history of fractures or low-impact fractures
- Smoking and excessive alcohol intake increase risk
Glucocorticoid therapy, medicine used to reduce inflammation, can increase bone loss and fracture risk. Other medications can too including proton pump inhibitor therapy, anticonvulsants, aromatase inhibitors, tamoxifen, Depo-Provera and steroids. Conditions that are associated with bone loss include gastrointestinal and autoimmune diseases, genetic issues, diabetes and others.
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Symptoms And Diagnosis Of Parkinsons:
Lets take a further look at Parkinsons disease.
Did you know that certain medical procedures, such as bone marrow transplants, can cause Parkinsons symptoms? Head trauma, liver disease, tumors, lesions, and vascular disease are all direct causes of Parkinsons disease. Physicians tend to be careful when testing for Parkinsons. Several different tests need to be done:
- The first test will be a blood test. The purpose is to test for toxins that may be causing the symptoms of Parkinsons.
- Next, an MRI and CT scan will examine the entire body and look for any unusual obstructions or abnormal functions in the vascular region.
Why Is There A Link
Since the 1970s, researchers believed that levodopa caused melanoma in people with Parkinsons.1,3,4 Levodopa impacts the bodys creation of melanin and melanocytes, leading scientists to blame this drug for a higher incidence of melanoma in people with PD. Many research studies have since reported that levodopa does not cause melanoma, but no one knows exactly why this association between melanoma and PD exists.2,4
Although the exact relationship between PD and melanoma is still a mystery, researchers have suggested many other reasons for this association, including social-environmental factors, immune system irregularities, and genetics.
Both PD and melanoma are associated with melanin 5. PD is caused by the death of dopamine-producing cells , while melanoma results from the overproduction of melanin-creating cells. Although these changes are different , both conditions result from melanin-related abnormalities. Therefore, some researchers believe that people with PD and people with melanoma share the same immune system irregularities2.
Melanoma and PD are associated with some of the same non-changeable, genetic factors, such as race, sex, and skin type. Your risk of PD and your risk of melanoma both increase if you are a man, if you are White, and/or if you have fair skin.6,7 Therefore, based on these genetic similarities, some researchers believe that the same genetic abnormality affects both people with PD and people with melanoma.1,3
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Parkinsons Connections To Breast And Prostate Cancer
There are some associations between PD and certain other cancers that you may have read about in the news, but these links remain tenuous and have not led to any change in screening procedures for people with PD. For example, some studies showed a small increase in breast cancer risk in people with PD, while other studies did not support this claim. Breast cancer screening recommendations for people with PD remain the same as for the general population.
During a clinical trial testing a medication called Entacapone, a member of a class of PD medications called COMT inhibitors, prostate cancer cases were slightly higher among those taking the drug as compared to those on placebo. This raised concerns about a connection between using Entacapone and developing prostate cancer. However, in subsequent studies, this association was not substantiated.
Tips and Takeaways
Sensitivity Analysis And Publication Bias
In sensitivity analysis, we recalculated the combined OR by omitting one study per iteration. Each study included in our meta-analysis showed no obvious influence on the effect size. Neither the funnel plot nor the publication bias was performed in any pooling analysis due to the included studies were less than ten.
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Research Delves Into Connection Between Melanoma And Parkinsons Disease
Advances in imaging may help gather more datasets on tumor development from a single experiment.
Researchers at Mount Sinai in New York are using advances in tissue preparation, imaging, image analysis, and registration to explore the biology underlying the well-known comorbidity between melanoma and Parkinsons disease . The project recently garnered a $100,000 pilot grant co-funded by the Michael J. Fox Foundation, also in New York, and the Melanoma Research Alliance, Washington, DC.1
Having melanoma increases risk for PD, and vice versa, said Deanna L. Benson, PhD. She is a professor of neuroscience at the Friedman Brain Institute and director of Microscopy and Advanced Bioimaging Core at Mount Sinais Icahn School of Medicine.
Epidemiological studies, usually from the PD perspective, have repeatedly shown an increased risk among patients with PD to have, develop, or have had melanoma, and vice versa.2-4 The link has been known for many years, Benson said. And we realized that nobody had really delved into it. Benson is collaborating with cancer researcher Jose Javier Bravo-Cordero, PhD, associate professor of hematology and oncology at Mount Sinai in New York.
We decided to work on this problem because we thought that maybe together, we could discover the biology that underlies this shared risk.
Disclosures:
Role Of Neuromelanin In Pd
In the SN, neuromelanin is responsible for the dark pigmentation of the dopaminergic neurons. In the brains of PD patients, loss of these dopaminergic neurons causes decreased levels of neuromelanin in the SN, but there has been no correlation reported in the levels of neuromelanin in the SN of PD patients of different race. It has been suggested that neuromelanin formation may be neuroprotective because it can scavenge toxic dopaquinone and help in sequestering metal ions such as copper, iron, cadmium and manganese in human nigral neurons. Lack of neuromelanin makes the neurons more susceptible to oxidative stress and leads to impairment of motor function . The lower occurrence of PD in the black population than in Caucasian populations suggests that, in analogy to the higher cutaneous melanin synthesis, there may be a higher neuromelanin synthesis in the black population, enhancing the protective effects in the SN against external toxic substances .
It has also been suggested that melanosis might protect against both PD and melanoma. This is supported by studies that show a negative association between tobacco smoking and PD . In smokers, melanosis occurs as a result of increased melanin synthesis because nicotine can stimulate activity of melanocytes and production of melanin or the capability of melanin to bind to noxious substances generated by tobacco smoke . Increased melanosis in smoking PD patients therefore may explain the protective effect of smoking against PD.
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F Prognosis And Patient Counseling
Parkinsons is a progressive disease, although the rate and degree of progression is variable. Treatments such as levodopa that initially provide great improvement in motor skills, tend to lose their effect or longevity with time.
There are many Parkinsons support groups that patients and their families can benefit from. There is currently no genetic testing recommended for family members.
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23 February 2018
J. William Langston, Jesse C. Wiley & Michele Tagliati
volume 12, Article number: 9254
An to this article was published on 14 September 2022
This article has been
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Common Genetic Associations Link Pd And Melanoma
Environmental toxins and genes interact and are presumably involved in PD. Lower detoxification enzyme activity may play a crucial role in pathogenesis of PD . The genes CYP2D6 and GSTM1 encode enzymes that have been reported to play important roles in responses of cells to endogenous and/or exogenous reactive intermediates, thereby influencing the susceptibility of an individual to developing PD . The presence of null polymorphism in the GSTM1 gene can result in the lack of expression of the enzyme, and can cause neuronal death that may contribute to PD . CYP2D6 is believed to be involved in PD because of its role in the regulation of drug and toxin metabolism, but studies linking the relation of PD to CYP2D6 are inconsistent . It has also been reported that polymorphisms in VDR are involved in PD pathogenesis . High frequency of polymorphisms of CYP2D6 or the polymorphism of VDR and null for GSTM1 gene, are found in melanoma patients as well, suggesting that variations in CYP2D6 and VDR or GSTM1 genes may increase the risk for both melanoma and PD. In addition it has been shown that mutations in PLA2G6 are also associated with both PD and melanoma , suggesting a further mechanistic link between PD and melanoma .
Fig. 1
Role Of Tyrosine Hydroxylase In Pd And Melanoma
The enzyme tyrosine hydroxylase is involved in the conversion of tyrosine to DOPA, the rate-limiting step in the biosynthesis of DA within dopaminergic neurons . In PD, there is a loss of TH in the striatum. The most effective treatment of PD is with the use of DOPA, DA agonists, or inhibitors of DA catabolism. However, an excess of cytosolic DA can form reactive intermediates, such as dopaquinone and reactive oxygen species that are associated with dopaminergic neuronal cell loss. Thus TH, an essential enzyme critical for synthesis of DA, also facilitates the formation of ROS that can cause oxidative stress leading to neuronal loss in PD . TH is also found in human melanoma cells . In skin melanocytes, TH is involved in catalyzing the conversion of tyrosine to DOPA, thereby generating the substrate and activator for tyrosinase, the enzyme that catalyzes the first and rate-limiting step in the biosynthetic pathway of melanin Fig 2.
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Melanoma And The Risk For Pd
In part 2 , the investigators identified 1544 patients diagnosed with melanoma between 1976 and 2014 and compared them with a control group of 1544 residents without melanoma to assess the prevalence of PD.
There were 43 cases of PD in the melanoma cohort and 14 cases of PD in the control group. Again, the researchers tweaked the numbers according to index dates. In the end, using a Cox proportional hazards model, the researchers found that the melanoma cohort had a 4.2-fold increased risk for PD after the index date compared with controls .
The Link Between Melanoma & Parkinsons
The relationship between melanoma and PD runs both ways: Specifically, people with PD are 4x more likely to develop melanoma, and people with melanoma have 4x the risk of developing PD.1 Even given these statistics, it is important to know that many people with PD will not develop melanoma, and many people with melanoma will not develop PD. However, if you are affected by either of these conditions, you should talk to your doctor about your risk factors.
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Melanoma Parkinson’s: See One Be Aware Of The Other
Nick Mulcahy
Patients with Parkinson’s disease have about a 4-fold increased risk of having preexisting melanoma and those with melanoma have a similar risk of developing PD, according to new retrospective, case-control analyses.
Despite the significantly heightened risks, the authors of the combined study stopped short of strongly recommending screening for all such patients.
Instead, they had less emphatic advice: “Physicians may consider counseling patients with melanoma about PD risk and implementing cutaneous and ocular melanoma surveillance in patients with PD.”
“I think that the results of the study have to be replicated by others before coming out with stronger guidelines,” said senior author, Jose Pulido, MD, MPH, from the Mayo Clinic in Rochester, Minnesota.
“In the meantime, I think that this should at least raise our awareness of the possible reciprocal association,” he told Medscape Medical News.
The new study was published in the July issue of Mayo Clinic Proceedings.
Dating back to the early 1970s, there has been speculation about the relationship between PD and melanoma, the authors write. The initial theory was that the PD drug levodopa created a risk for the skin cancer. But subsequent randomized controlled trials and prospective studies did not confirm the hypothesis.
However, multiple other studies have since found an increased risk for melanoma in patients with PD, including a 7-fold increase in a recent prospective North American study .
People With Parkinsons Should Be Monitored For Melanoma And Vice Versa Mayo Study Finds
ROCHESTER, Minn. People with the movement disorder Parkinsons disease have a much higher risk of the skin cancer melanoma, and vice versa, a Mayo Clinic study finds. While further research is needed into the connection, physicians treating one disease should be vigilant for signs of the other and counsel those patients about risk, the authors say. The findings are published in Mayo Clinic Proceedings.
Overall, patients with Parkinsons were roughly four times likelier to have had a history of melanoma than those without Parkinsons, and people with melanoma had a fourfold higher risk of developing Parkinsons, the research found.
Medical experts have speculated about the relationship between Parkinsons and melanoma for decades, with varying conclusions, the Mayo researchers note. Several studies have suggested levodopa, a drug for Parkinsons, may be implicated in malignant melanoma, but others have found an association between the two diseases regardless of levodopa treatment, they add.
Future research should focus on identifying common genes, immune responses and environmental exposures that may link these two diseases, says first author Lauren Dalvin, M.D., a Mayo Foundation Scholar in Ocular Oncology. If we can pinpoint the cause of the association between Parkinsons disease and melanoma, we will be better able to counsel patients and families about their risk of developing one disease in the setting of the other.”
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