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Risky Business: Nongenetic Factors May Increase Odds of Developing ALS

Everyone is born, and everyone dies. What happens in between — colds and flu, cardiac problems, cancer, amyotrophic lateral sclerosis (ALS) — is anyone's guess. And people do guess. It's common — indeed, almost universal — after receiving a diagnosis for any condition to question whether there's something that could have been done to prevent it.

In some cases, what a person does or doesn't do has no bearing on whether or not they develop a disease later in life. This is because their DNA (genetic "blueprint") may feature certain mutations or variants that cause them to develop the disease, or that raise the risk of developing it. For example, certain mutations in the SOD1, TDP43, FUS and C9ORF72 genes are known to cause ALS, while other genetic flaws such as expansions in the ataxin 2 gene, extra copies of the SMN1 gene and repeat expansion mutations in the NIPA1 gene are associated with a higher risk of developing the disease.

However, some diseases can be caused, at least in part, by things that can't be found in a person's genetic makeup — nongenetic risk factors.

For example, an unhealthy diet is often pinpointed as the cause for certain types of heart disease, and too much exposure to the sun has been identified as a cause of some kinds of cancer.

So, what about ALS? Is there something besides people's genes that can cause the disease, or increase the chance of developing it? What are some of the possible nongenetic risk factors for ALS, what is known about them and what are scientists doing to learn more?

Do nongenetic risk factors contribute to ALS?

Currently, only a small percentage of ALS is clearly attributable to genetics, leaving a lot of room for the possible involvement of nongenetic factors.

Age and gender are consistent and accepted nongenetic ALS risk factors. Older age is positively associated with the risk of developing ALS, and men are slightly more likely to develop ALS than are women. Studies suggest an overall ratio of about 1.2 men to every woman who develops the disorder.

One hint that the environment also may play a role is the history of ALS in Guam, where incidence of the disease between 1940 and 1965 reached 50 to 100 times its worldwide rate and became the leading cause of death among natives.

Most ALS in Guam at that time was associated with Parkinson-dementia complex (PDC), a disorder that combines the tremor of Parkinson’s disease with the memory loss of Alzheimer’s. ALS-PDC wasn’t found among non-native Guamanians.

The high rates of ALS on Guam have since been attributed to inclusion in the native peoples’ diet of poisonous nuts from the indigenous cycad tree, and the incidence of both ALS and ALS-PDC among the native Gaumanians has dropped dramatically over the course of several decades. Such rapid change isn’t consistent with genetics and is a powerful indicator that the environment played a key role in causing the disease.

Risk in the environment

Nongenetic risk factors for disease may exert influence alone or in combination.

Common environmental factors suspected of contributing to ALS include ethnicity, geographic location, diet and nutrition, exercise and sports, alcohol or tobacco use, occupation, electric shock, exposure to chemicals or radiation, and concussion or other physical injury ("trauma").

Some suspicion also falls on: air, water or soil pollution; electromagnetic fields; the materials used in the construction of houses and roads; land management techniques; agricultural methods, including irrigation practices; climate and climate change; economic status and availability of health care.

Join a registry

Epidemiology — from the Greek, meaning "the study of what is upon the people" — is the study of the patterns, causes and effects of human health and disease.

Epidemiologists design and conduct studies, collect and analyze data, and often help interpret and disseminate their findings. (Read ALS Research: Q&A with Marc Weisskopf to learn more about epidemiological research in ALS.)

What epidemiologists learn about the nature of disease is used in the practice of medicine and therapy development, and informs policy decisions relating to public health.

One way people can help epidemiologists identify ALS risk factors is by participating in registries that collect information on demographics and lifestyle factors, and biorepositories that collect biological samples.

For more, see the sidebar below and also these registries: fALS ConnectNational ALS Registry and MDA's Clinical Neuromuscular Disease Registry.

And for more on the search for nongenetic factors, read an interview with ALS researcher Marc Weisskopf.

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