The findings of a new study could be a game-changer for cancer prevention research. The immune system may play a much more important role in age-related cancer risk than previously thought.

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The thymus gland (shown here) may play a role in cancer risk.

Each year, more than 8 million people die of cancer globally. Although treatments are steadily improving, there are still many questions unanswered.

Essentially, cancer is caused by a succession of gene mutations that accumulate over time.

We know that some factors can increase the rate at which these genetic mutations occur, and thus increase the risk of cancer. These factors include smoking tobacco, drinking alcohol, and obesity.

However, not all risk factors are avoidable; one major risk factor is getting old. As our age increases, so does our cancer risk. Why does aging increase cancer risk so significantly? A multidiscipline research group recently provided an unexpected new answer to this question.

It stands to reason that, as time marches on, the likelihood of mutations increases. Until now, that has been the standard explanation: the older you get, the more mutations you have, and your cancer risk is greater.

A recent study — conducted at the University of Dundee in the United Kingdom, and with help from the Curie Insitute in Paris, France, as well as Heriot-Watt University and the University of Edinburgh, both in the U.K. — questions whether this is the whole story.

The hypothesis the team set out to prove was that cancer risk increases with age due to an aging immune system. It is well-known that the immune system becomes less effective as we get older, making us more susceptible to illness.

Could it also increase cancer risk? Their findings are published this week in the Proceedings of the National Academy of Sciences.

The thymus gland, which is an organ of the immune system, is involved in nurturing and developing T cells, which are major players in the immune system. Much of the decline in the immune system’s strength over time is due to the thymus’s steady deterioration.

Despite its importance in our younger years, the thymus begins to shrink from the age of 1. It halves in size every 16 years, and the production of T cells follows suit. The authors of the new paper wondered whether this decrease in capacity might play a role in cancer risk.

The researchers took data from the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results program. In all, they included 2 million cancer cases in people aged 18–70.

Next, the team designed a mathematical model that predicted how cancer rates would rise if they were related to a declining immune system. They compared their findings with real-life data.

The researchers found that their model fitted the data more tightly than the standard so-called multiple mutation hypothesis.

As study leader Dr. Sam Palmer explains, “The immunosurveillance hypothesis is that cancer cells are continually arising in the body but that normally the immune system kills them before a new tumor is able to establish itself. The T cells are constantly scanning for cancer cells, looking to destroy them.”

If they can’t find them soon enough or the immune system is weak, then the cancer population has the chance to grow. The chances of this happening will increase with age as the thymus is shrinking all the time.”

Dr. Sam Palmer

He provides more information about how their model might work, saying, “[W]e imagined a war between T cells and cancer cells, which the cancer cells win if they grow beyond a certain threshold.”

“We then set this threshold to be declining with age, proportional to T cell production,” Dr. Palmer added. “This simple hypothesis turns out to be able to explain much of the cancer incidence data.”

Age-related cancer risk increases more steeply in men compared with women. Because the thymus declines more rapidly in men than women, this might account for this difference, which the multiple mutation hypothesis theory cannot account for.

When the gender differences were explored, the risk profiles between men and women fitted more neatly with the model’s data than with the traditional theory.

Of course, this study was based on a mathematical model and will therefore need to be replicated in the real world. But it’s certainly food for thought.

As senior study author Dr. Thea Newman says, “This is still very early days, but if we are proven right then you could be talking about a whole new way to treat and prevent cancer.”

She adds, “Nearly all of the mainstream research into cancer is based on how we can understand genetic mutations, target them, and thereby cure the disease.”

We’re not debating the fact that mutations cause cancer,” continues Dr. Newman, “but are asking whether mutations alone can account for the rapid rise in cancer incidence with age when aging causes other profound changes in the body.”

Thymus expert Prof. Clare Blackburn, at the University of Edinburgh, discusses the potential future implications. She says, “In addition to mutations, this suggests we should also focus on how to boost thymus function in a controlled way, perhaps by transplantation or by controlled regeneration, so we can increase the number of T cells we are making.”

“Of course,” she adds, “we also need to look at whether there may be unintended consequences of doing this, and how to minimize these if they occur.”

These findings are fascinating and open up a new avenue for cancer researchers to explore. This team of biology, physics, and computer science researchers may have provided a vital first step toward new cancer prevention strategies.