Tag Archives: cancer

A Causal Link Between Alzheimer’s Disease and Cancer

Though they may seem like unrelated diseases, cancer and Alzheimer’s disease are more closely linked than you’d expect. As I’ve discussed previously on the blog, scientists have been aware for nearly 15 years that these two conditions are inversely correlated. In other words, cancer survivors have a lower risk of later developing Alzheimer’s disease, and vice versa.

According to one meta-analysis, Alzheimer’s patients have a 42% reduced risk of developing any kind of cancer in their lifetime, while cancer survivors have a 37% reduced risk of Alzheimer’s disease. Notably, this correlation is not caused by decreased life expectancy or different lifestyle choices, as the analysis took these factors into account in their calculations.

While those numbers look pretty convincing, we must be careful when interpreting the results of observational studies. A scientist’s favorite mantra is “correlation does not imply causation.” In other words, based on these studies alone, we have no way to know whether cancer directly protects against Alzheimer’s disease, Alzheimer’s directly protects against cancer, or some unknown third factor is linking the two diseases indirectly. We can’t determine a causal relationship from observation alone.

However, a recent study published in Scientific Reports attempts to address this dilemma. Researchers from the University of Cambridge used a technique called Mendelian randomization to determine causality. Essentially, this involves searching for genetic variants that are known to increase the risk of cancer, and then determining whether those same variants also decrease the risk of Alzheimer’s. By probing at the genetic level, this technique allows researchers to directly determine whether cancer is protective against Alzheimer’s.

Using data from public repositories, the authors determined that several genetic variants involved in cancer risk are protective against Alzheimer’s. Overall, a 10-fold (1000%) higher genetic risk for developing cancer results in a 2.5% reduced risk of Alzheimer’s. That may seem like a small reduction, but keep in mind that this represents only the genetic component of risk. Since both cancer and Alzheimer’s are complex diseases and heavily influenced by non-genetic factors, these numbers encapsulate only a small portion of an individual’s overall risk.

Importantly, this study is the first to show a causative link (rather than merely a correlation) between Alzheimer’s disease and cancer. The study’s lead author, Sahba Seddighi, stated, “Our results offer novel possibilities for targetable pathways in Alzheimer’s disease—which remains without a cure, despite a rapidly growing aging population—and call for a deeper understanding of the underlying mechanisms behind this relationship.”

So what does this link really mean? In a way, it makes some intuitive sense: cancer is the result of uncontrolled cell growth and proliferation, while Alzheimer’s is associated with cell death and degeneration. But what genetic interactions and cell signaling pathways are involved remains unknown.

In the meantime, by shedding new light on the genetic underpinnings of Alzheimer’s, the study brings a new insight to the field, which will hopefully bring scientists one step closer to finding a cure.

 

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The Strange Link Between Alzheimer’s and Cancer

Two of the most common causes of death in America are Alzheimer’s disease and cancer. To most of us, these seem like completely unrelated diseases. However, this intuition is far from the truth. For reasons that puzzle scientists, having Alzheimer’s actually seems to protect you from cancer, while having cancer may protect you from Alzheimer’s.

This counterintuitive relationship was first discovered in 2005 by the Washington University Alzheimer’s Disease Research Center. This study of 882 elderly participants reported that the people with Alzheimer’s disease were significantly less likely to be diagnosed with cancer during the course of the study, and that those who did develop cancer did so at an older age. In 2012, the Framingham Heart Study reported that participants with Alzheimer’s disease were less than half as likely to be diagnosed with cancer during the course of the study compared to dementia-free subjects of the same age, sex, body mass index, and smoking status. A 2014 meta-analysis summarized the results of six independent papers to conclude that Alzheimer’s patients have a 42% reduced risk of cancer in their lifetime, while cancer survivors have a 37% reduced risk of Alzheimer’s. These differences remained statistically significant even after accounting for the effects of reduced life expectancy and demographic factors.

Interestingly, this inverse relationship does not seem to apply to other diseases of the central nervous system, including vascular dementia, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), or Down’s Syndrome. This suggests that the cancer-protective mechanism is specific to Alzheimer’s disease. Weirdly, the naked mole rat is immune to both cancer and Alzheimer’s, which may help to shed light on this strange connection. (Read more: What Naked Mole Rats Can Teach Us About Alzheimer’s Disease)

Scientists are still unsure as to why cancer and Alzheimer’s are inversely related, although several theories have been suggested. One possibility is that proteins that are needed for cells to divide and reproduce might be under-produced in Alzheimer’s patients, causing a reduction in neurogenesis (the formation of new brain cells, important for learning and memory) while also protecting from cancer by preventing uncontrolled cell division. Another theory is that amyloid beta, the protein that forms toxic clumps in the brains of Alzheimer’s patients, may fight cancer by suppressing the growth of tumors. The APOE4 allele, which increases the risk of Alzheimer’s disease, has also been associated with a reduced risk of certain cancers. Further research is needed to establish a definite mechanism.

One of the main consequences of this relationship applies to clinical trials of drug candidates to treat Alzheimer’s disease (see Where’s our cure to Alzheimer’s disease?). Several trials have had to discontinue prematurely due to an increased risk of cancer among the participants, especially skin cancers. In other words, the drugs that were supposed to be combatting Alzheimer’s disease ended up causing some participants to develop cancer. Though only a subset of trials have reported this problem, it’s worth being aware of the possibility when considering whether to participate in a clinical trial, particularly if your family has a history of skin cancer or other cancers.

References

Catala-Lopez, F., et al. Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies. Psychother Psychosom. 2014;83(2):89-105. Link
Driver, J.A., et al. Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ. 2012;344:e1442. Link
Ma, L.L., et al. Association between cancer and Alzheimer’s disease: systemic review and meta-analysis. J Alzheimer Dis. 2014;42(2):565-573. Link
Roe, C.M., et al. Alzheimer disease and cancer. Neurology. 2005;64(5):895-898. Link
Roe, C.M., et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology. 2010;74(12):106-112. Link
Slattery, M.L., et al. Associations between apoE genotype and colon and rectal cancer. Carcinogenesis. 2005;26(8):1422-1429. Link

 

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