Since the 1950s, scientists have drawn three conclusions about the relation between allergies and cancer: Compared with people who don’t have allergies, allergy sufferers have (1) a higher risk of cancer, (2) a lower risk of cancer and (3) the same risk of cancer.

A recent review of the studies, published by scientists at Cornell University, pinpoints a nuance that could explain the apparent contradiction. Study authors Paul Sherman, Janet Sherman and Erica Holland analyzed the results of more than 600 studies published since 1955 on the correlation between allergies and cancer. Like some of their predecessors, the authors found that, with the exception of asthmatics and lung cancer, allergy sufferers do not tend to have a higher risk of cancer, as had often been assumed. In fact, they found that allergy sufferers have a lower risk of cancer that occur in those tissues exposed to substances from the outside world, like those of the throat and skin. The Shermans and Holland also suggest that how the body reacts to allergens forces out carcinogens that could have later caused cells to become cancerous.

This new finding, Paul Sherman says, provides evidence to support the prophylaxis hypothesis, a little-researched theory first proposed in 1991 by the controversial evolutionary biologist Margie Profet. According to the hypothesis, allergy symptoms like sneezing and watery eyes evolved through natural selection to expel foreign particles containing carcinogens from the body—much like turning on a firehose to clean a sidewalk—and thus reduce the occurrence of cancer.

Two Dueling Theories
Not all scientists think the prophylaxis hypothesis has merit. Manuel Penichet, an immunologist and microbiologist at the University of California at Los Angeles and one of the leading scientists in allergo-oncology, says another major allergy-cancer hypothesis, called immunosurveillance, may be taking place.

Immunosurveillance, a theory first suggested by Frank Macfarlane Burnet in 1957, posits that allergic reactions alone do not protect the body from cancer. Rather, the same immune cells that cause allergy symptoms might also eradicate cancerous and precancerous cells before they further develop, Penichet explains. Instead of using a firehose to keep things clean, the immune system might just spray the area with molecular bullets.

In most cases, the allergy mechanism works like this: Loose allergens enter the body’s tissues, often through cavities such as the nose. The allergens come into contact with immunoglobulin E (IgE) antibodies—a specific class of large Y-shaped proteins involved in the allergic response. IgEs are usually linked to mast cells, which are large storage containers for chemical mediators and enzymes. When IgE encounters an allergen, the antibodies tell the mast cells to open the levees, unleashing chemicals that induce allergic symptoms, such as watery eyes, that help eradicate the perceived threat. If prophylaxis is to be believed, this wave of body fluids should be enough to indirectly prevent cancer by washing away carcinogens carried on the allergen. If immunosurveillence is correct, it’s the overactivated immune system itself, not the runny nose, that directly kills cancer cells.

More research must be done to determine if IgE has a direct role in eradicating cancer cells. “There are a few back associations that people have attempted to make,” says Jordan Orange, an associate professor of pediatrics at the University of Pennsylvania who specializes in immunology. But he remains skeptical because patients who are deficient in IgE molecules do not have higher rates of cancer than those with normal IgE levels.

Capitalizing on the Link
Despite the uncertainties, scientists are working on ways to exploit different components of the immune system, including classes of immunoglobulins other than IgE, to protect the body from cancer. For instance, the San Francisco biotech company Genentech received FDA approval in 1998 to sell a drug called Herceptin, an antibody that binds a protein that when overproduced is believed to contribute to breast cancer. The antibody-binding renders the protein ineffective and prevents the breast-cancer cells from growing. And in April, the FDA approved Provenge, made by the Seattle firm Dendreon. Provenge is the first treatment that helps the immune system kill cancer cells. The procedure sensitizes a patient’s white blood cells to a protein that contains prostatic acid phosphatase, which is emitted by prostate cancer cells. The white blood cells guide the immune system to the cancerous cells, which are then eradicated by a host of specialized cells and proteins.

Meanwhile, Penichet and a team at UCLA are exploring whether IgE itself can be used to combat cancer. They are working with antibodies that target molecules expressed by various cancers and are currently studying the effects of these antibodies in mice.

For now, Paul and Janet Sherman hope doctors will reconsider how they treat allergies. “Until recently, people haven’t asked why allergies are there,” Janet Sherman says. “They just thought it to be an annoying phenomenon that needs to be eliminated.” It seems allergies may not be malfunctions of the immune system but rather an important facet of the body’s defenses.

Background
Close to Half of Us Have Allergies

Allergies arise when the immune system reacts strongly to something that is not directly dangerous to the body, such as pollen, house-dust mites, bee stings, or certain foods or drugs.
The mucus membranes and skin that come into contact with the allergens respond by watering or itching, and the reaction is manifested in such forms as hay fever, asthma, hives or rashes. About half the population of North America suffers from some kind of allergy.