The human immune system is an incredibly complex web of cells, tissues and organs that defend the body by responding to pathogens — outside invaders that could harm the body. When a virus, bacteria, fungus or other foreign agent enters the body, the immune system leaps in to fight off the threat.
Inflammation is part of this immune response and arises because the immune system has released white blood cells to surround and protect the compromised area. Acute inflammation may be uncomfortable for the patient, but it’s the body’s helpful way of dealing with an injury or an infection — those white cells and other chemicals released during that immune response help repair damage and fight infection.
However, inflammation can become a chronic condition in response to toxins from the environment, an autoimmune disorder and other triggers. When the body tries to cope with a constant influx of toxins such as cigarette smoke, chronic inflammation may develop as the body’s effort to try to reduce damage. Over time, chronic inflammation can become a health problem of its own, and it has been associated with an increased risk of developing various forms of cancer. The National Cancer Institute reports that “chronic inflammation may be caused by infections that don’t go away, abnormal immune reactions to normal tissues, or conditions such as obesity. Over time, chronic inflammation can cause DNA damage and lead to cancer.”
[See: 7 Things You Didn’t Know About Lung Cancer.]
Inflammation and the immune system are also implicated in two common conditions that affect the lungs: asthma and allergies.
The National Heart, Lung and Blood Institute reports that “asthma is a chronic lung disease that inflames and narrows the airways. Asthma causes recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath and coughing.” More than 25 million people in the U.S. have asthma. Inflammation of the airways is a major feature of asthma, which leads to hypersensitivity and overreactivity of the lungs and airways to triggering pathogens or stimuli. This causes a narrowing of the airways and makes it harder to breathe.
In allergies — primarily seasonal respiratory allergies — exposure to an allergen such as pollen, pet dander or dust can also trigger inflammation and asthmatic symptoms in some people. The Asthma and Allergy Foundation of America reports that “allergies are one of the most common chronic diseases,” and they occur “when the body’s immune system sees a substance as harmful and overreacts to it.” This triggers a cascading response, including the release of histamine and an antibody called immunoglobulin E. “These antibodies respond to allergens,” but they can cause the person to experience a variety of symptoms, including wheezing, itchy and watery eyes, coughing, sneezing and other respiratory problems.
The immune system’s involvement and the development of inflammation in response to both these conditions and inflammation’s known involvement in cancer raises the question: Does having asthma or respiratory allergies put a person at higher risk of developing lung cancer later in life?
“It’s an interesting question,” says Dr. Andrea B. McKee chair of radiation oncology at Lahey Hospital &Medical Center‘s Sophia Gordon Cancer Center in Burlington, Massachusetts. “There really is not a lot out there about seasonal allergies and asthma” and their relationship to lung cancer risk, she says. But she notes a connection has been drawn between asthma and chronic obstructive pulmonary disease and pulmonary fibrosis, two chronic conditions “within the spectrum of inflammatory disorders of the lung” that also make it hard to breathe and feature lots of inflammation in the lungs.
Patients with COPD do have a higher risk of developing lung cancer. A large, global study conducted at the Harvard T.H. Chan School of Public Health in Boston measured a 1.86-fold higher risk of small cell lung cancer in patients with COPD. (SCLC accounts for about 15 percent of all lung cancer cases.) Having COPD has also been found to be a risk factor for developing non-small cell lung cancer, which is the most common form of lung cancer. A major reason for this shared connection is a history of smoking cigarettes, which is the No. 1 risk factor for developing both COPD and lung cancer. But according to a 2016 study, “40 to 70 percent of lung cancer patients also have COPD and the risk of COPD is sixfold higher in lung cancer patients than in matched smokers, leading to the conclusion that COPD and lung cancer must share risk factors other than tobacco exposure.” These additional risk-elevating factors could include genetics or inflammation, but must be studied further to determine an exact correlation.
[See: What Not to Say to Someone With Lung Cancer.]
One of the challenges associated with studying the connection between allergies and lung cancer is that “allergies are so common,” and they may come and go during a person’s lifetime, McKee says. It’s difficult to do the kind of long-range epidemiological studies that a firm answer requires “when you have something that’s just so pervasive. It’s everywhere, and it’s a difficult area to quantify and evaluate.” There’s also a wide range of individual responses to allergic triggers, so it can be difficult to quantify exactly what’s meant by an allergy when doing a large study.
However, some researchers are attempting to do just that and are beginning to lay the groundwork for an interesting new area of inquiry called allergooncology. “It’s a very new area,” says Sara Huerta-Yépez, a researcher working on deciphering the cross-links among asthma, allergies and lung cancer jointly at the Hospital Infantil de Mexico, Federico Gomez, in Mexico City and at the UCLA Pathology & Laboratory Medicine Department at UCLA Health.
So far, what studies have been completed (in cells and mouse models, not people) have shown some conflicting results, but what’s interesting is that in some studies, having allergies or asthma — or more precisely the higher levels of the antibody IgE and another immune system–generated protein called transforming growth factor beta — might actually reduce cancer risk. TGF-? is a cytokine, or protein, that controls cellular growth and proliferation, and it is often observed in higher levels in individuals with allergies or asthma.
Although it’s been shown in other studies that the presence of TGF-? could actually encourage tumor growth, in recent studies, Huerta-Yépez showed that TGF-? might actually protect against the progression of cancer, but only when it’s involved in allergic inflammation. “TGF-? has at least two roles. When TGF-? is increased in allergic inflammation, it can decrease the tumor progression,” but that allergic environment must be present, she says. This was measured by inducing asthma in one group of animals and injecting cancer cells, while another group without asthma was administered cancer cells. “In both groups, TGF-? increased, but in the group with both asthma and cancer, the tumor growth was decreased in a significant manner,” she says. “If you inhibit the expression of TGF-?, the tumor starts to progress again.”
Huerta-Yépez says that IgE has also been shown to have tumor-inhibiting properties. “There are two types of asthma: allergic asthma or non-allergic asthma. The most common is allergic asthma, so when you talk about allergies, you have to think about IgE antibodies,” which are released in response to allergens, she says. “IgE is a very important marker for allergies.” In an ongoing study that has not yet been completed, Huerta-Yépez is investigating the role of IgE in more detail and says that the levels of IgE appear to correlate to tumor activity. “That means if it’s a low IgE concentration, it’s a worse kind of cancer. Higher levels of IgE appear [to correspond] with less aggressive types of cancer.” Other cytokines and compounds released by the immune system may also play a role.
She’s also currently looking into whether there’s a difference in the type of cancer cells used. In some studies, breast cancer cells were used to study whether asthma, allergies and cancer coexisted, but Huerta-Yépez says she wants to determine whether the effect is the same when the target organ is the same — asthma occurs in the lungs as does lung cancer, so it stands to reason that the type of cells involved could influence the outcome.
Although still in their very early days, these investigations could potentially reveal new targets for developing therapeutic agents to treat lung cancer. Huerta-Yépez says this is a line of inquiry she’s chasing in her lab, but says difficulty arises when trying to harness specific elements of the immune system to fight cancer because it can trigger unintended side effects or even an autoimmune disorder. “Some cytokines can be very difficult to become a target because they are playing an important role in a normal system,” and until we understand all aspects of that role and how it might impact other elements of health, it’s difficult to develop a therapy based on that one observed protective function.
[See: 7 Innovations in Cancer Therapy.]
In addition, she notes that there’s a lot of variation from person to person and from region to region in how the immune system works. “Every human has a different immune system activity,” and the local environment can trigger different aspects of the immune system to turn on or off. “Maybe in Mexico [where her studies have been conducted], we can say allergies protect you from lung cancer. But in Italy it may be different. A different environment can activate or suppress the immune system because the immune system depends on the food, it depends on the exposure to allergens, it depends on genetics, and it depends on stress — obesity down-regulates the immune system.” That’s why so much more work needs to be done before we have a definitive answer to the question about whether and how allergies, asthma and lung cancer intersect.
Nevertheless, Huerta-Yépez says she thinks the field of allergooncology will offer more data about a potential cross-link among these conditions in the future that may help us better understand both the immune system and how lung cancer develops. For the moment, she says based on her research, which has been done solely in cells and animal models, not in people, she believes that “at least with some kinds of cancer, such as breast cancer and lung cancer, I can say that [having] asthma or allergies protects against tumor growth.”
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Does Having Allergies or Asthma Increase My Risk of Lung Cancer? originally appeared on usnews.com
