Inflammation and Chronic Disease - Part 2: Cancer

The role of inflammation in the genesis of cancer is a complex and seemingly paradoxical issue. As mentioned in last week's health tip, inflammation is part of a process that helps the body remove damaged cells, irritants or germs following injury, exposure or infection. Cancer cells generally fall into the "damaged cells" category and are destroyed by an inflammation-stimulated immune system. In some cases, however, particularly when the inflammation becomes persistent, the opposite occurs and inflammation contributes to the development of cancer.

Cancer can also develop from chronic infection. Infection, in contrast to inflammation, is caused by an organism, such as bacteria, viruses, or fungi. An inflammatory response is one of the steps that the body normally takes to rid itself of an infection. When certain infections become chronic, however, the associated persistent inflammation may set the stage for the development of cancer.

Recently, research has shed some light on how inflammation could lead to the development of cancer. Inflammation can cause a drop in several proteins that are involved in DNA repair. This leads to a higher rate of gene mutations, some of which are responsible for cancer development. The following are a few of the most well-known cancers that have persistent inflammation as an associated cause.

Colon cancer: High fat diets, sedentary life style, genetic factors, and cigarette smoking are known to be the most common causes of colon cancer. However, two inflammatory conditions of the bowel---ulcerative colitis and Crohn's disease (both of unknown causes)---are also known to impose an increased risk of developing colon cancer. Whereas, most colon cancer begins as a small growth called a polyp, colon cancer associated with inflammatory bowel disease typically involves larger areas of the colon, often necessitating removal of the entire colon for treatment.

Cervical/Throat Cancer: Cervical cancer, occurring in the lower portion of the female uterus, is usually caused by a human papillomavirus (HPV) infection. Over half of the cases of throat cancer are also related to this infection. Most HPV infections are cleared by the body. When the body's immune system is unable to get rid of a high-risk HPV infection, it becomes chronic and can lead to the development of cancer.

Liver cancer: Long term alcohol abuse can lead to irreversible scarring of the liver, a condition known as cirrhosis. The combination of alcoholism and cirrhosis is known to increase one's risk of developing liver cancer. This increased risk, however, is small in comparison to the risk imposed by chronic viral hepatitis. Worldwide, chronic hepatitis B and C are responsible for 80% of cases of liver cancer, resulting in thousands of deaths each year. Unfortunately, chronic hepatitis, particularly that caused by the hepatitis C virus, can go undetected for years.

Stomach cancer: A bacterial infection of the lining of the stomach wall caused by Helicobacter pylori (H. pylori) is a well-known cause for ulcer symptoms. This same infection has been found to double the risk of developing cancer of the stomach. Although not yet proven, it is believed that treatment of the bacterial infection with a combination of antibiotics is effective in eradicating this risk.

Lung cancer: Worldwide, over one million people die from lung cancer each year. Up to 90% of this cancer can be attributed to cigarette smoking. One of the major factors in the development of lung cancer is inflammation brought on by repeated exposure to tobacco smoke. Other lung irritants, including silica dust, asbestos and coal dust, also appear to promote the development of lung cancer through an inflammatory pathway.

Having a disease or risk factor associated with the development of an inflammation-related cancer does not mean that cancer is inevitable. It does mean that the odds of cancer occurrence are higher and that special measures should be taken to reduce the risk, or to detect the cancer in as early a stage as possible. The relationship between inflammation and cancer is the subject of ongoing research. Important issues to be addressed in the future include:

• Developing vaccines for infectious diseases associated with chronic inflammation. Hepatitis B vaccine is currently available and a hepatitis C vaccine is in development. The HPV vaccine holds promise to further reduce the incidence of HPV-related cancers.
  
  
• Detecting asymptomatic disease, such as H. pylori infection of the stomach or hepatitis C, so that early treatment can be offered.
  
  
• Learning how often and how best to screen for certain cancers. It has been determined that the longer someone has a chronic inflammatory condition, the greater the likelihood of developing cancer. Information like this is taken into account when considering appropriate screening intervals.
  
  
• Developing medications to reduce inflammation. There is some evidence to support taking aspirin to prevent colon cancer in certain individuals. Additionally, the non-steroidal anti-inflammatory medicine, celecoxib, can reduce the number of pre-cancerous polyps that develop in patients with a condition known as familial adenomatous polyposis.
  
  
• Encouraging preventive measures, for example smoking cessation, when an unhealthy habit is clearly related to the inflammatory cancer.

Inflammation and Chronic Disease - Part 1: Cardiovascular Disease

Recently, I ran across a method of classifying foods based on their potential to cause inflammation in the body. The significance of this is that inflammation is thought to be the underlying cause for a number of illnesses including diabetes, coronary artery disease, as well as several types of cancer. Even though some people (including the author of the dietary guide that included the Inflammation Rating) are convinced that inflammation is the underlying cause of many chronic illnesses, there is still much to learn about the relationship between these two entities.

What is inflammation? Inflammation occurs as a normal part of the healing process. It is a process that allows the body to remove damaged cells, irritants, or germs following injury, exposure or infection. The classic signs of inflammation include redness, swelling, increased heat, and pain. The inflammatory response is what allows the skin to heal following a cut and is the primary cause of symptoms of the common cold as the body fights off the cold virus. Inflammation is different than infections, which are caused by organisms such as bacteria, viruses, or fungi.

How does inflammation relate to heart disease? Research is ongoing to determine the exact relationship between inflammation and the development of cardiovascular disease. The current theory goes something like this: certain factors, such as obesity, cigarette smoking, and high cholesterol are thought to "injure" blood vessels of the cardiovascular system. This damage can lead to atherosclerosis, the build-up of fat deposits in the walls of blood vessels. In an effort to "fix" the damage, the body's immune system swings into action, producing an inflammatory response. If people continue their unhealthy habits, atherosclerosis and its associated inflammation progresses, ultimately resulting in heart attack or stroke.

How do you measure inflammation in the body? One way of determining if inflammation is present in the body is to perform a blood test for C-reactive protein. This is a substance produced in the liver as a response to inflammation. While elevated C-reactive protein levels have been correlated with the presence of coronary artery disease, other inflammatory conditions can cause elevations of the C-reactive protein also. These include rheumatoid arthritis, certain cancers, and infections.

Who should be tested for C-reactive protein? Some doctors use C-reactive protein levels routinely when assessing patients for the heart disease risk, but this is not a universally accepted practice. The U.S. Preventive Services Task Force has rejected the C-reactive protein as a standard screening test since there is insufficient evidence that reducing the C-reactive protein can reduce the risk of heart attack and stroke. The American Heart Association, on the other hand, recommends a high-sensitivity C-reactive protein test (hs-CRP) as part of routine screening for those with other major risk factors for the development of cardiovascular disease.

Can inflammation be reduced? There is strong evidence that obesity, and especially excess fat in the abdominal region, is a major cause for the development of the metabolic syndrome which includes glucose intolerance (the precursor to diabetes) and elevated cholesterol. These conditions can cause damage to the blood vessels with resulting inflammation. Weight loss, with reduction of abdominal obesity, has been shown to lower C-reactive protein levels and presumably the associated inflammation. Cholesterol-lowering medications called statins also appear to reduce inflammation, perhaps by reducing damage to blood vessels from high cholesterol. Dietary management emphasizing the inclusion of sources of monounsaturated fats (extra-virgin olive oil), omega-3 fatty acids ("oily" fish such as salmon), fruits and vegetables (particularly berries, tomatoes, orange and yellow fruits, and dark leafy greens), with the exclusion of "inflammatory foods", such as margarine, high fat cheese, and marbled beef, has also been proposed as a way to reduce inflammation in the body.

Research is being conducted to see if other medications or dietary interventions can help lower indicators of inflammation and reduce the risk of heart disease. For now, the most critical issue when someone is found to have signs of excessive inflammation as with an elevated C-reactive protein is to control the modifiable risk factors for cardiovascular disease. These include cigarette smoking, high cholesterol, hypertension, obesity, and diabetes.

Calming Restless Leg Syndrome

Occasionally, medical complaints can be so vague or bizarre that it inhibits those suffering such symptoms from reporting them to their doctors. Restless leg syndrome (RLS) is such a disorder. RLS is neurological condition that is characterized by unpleasant sensations in the legs, and an uncontrollable urge to move the legs in an effort to relieve these feelings. It may alternately be described as an aching, burning, "pins and needles," or a "creepy crawly" sensation in the legs. The sensations are particularly bad at rest or when trying to go to sleep. Characteristically, RLS symptoms lessen by moving the legs. People with this disorder try stretching, walking, pacing or exercising in an attempt to combat the uncomfortable sensation in their legs. This irresistible urge to move the legs is where the name comes from. RLS affects up to 10% of the US population, with men and women being equally affected. RLS may begin at any age, but most of those who are affected severely are middle-aged or older. Childhood RLS is estimated to affect almost 1 million school-age children.

What causes RLS? In most cases, the cause of RLS is unknown. A family history of the condition is found in approximately half suffering this condition, suggesting a genetic tendency. In some cases, an underlying medical condition is responsible. These conditions include iron deficiency anemia, diabetes, kidney failure, and pregnancy.

How is RLS diagnosed? There is no single diagnostic test for RLS. The disorder is diagnosed clinically by evaluating the patient's history and symptoms. The four major criteria used to make the diagnosis are: (1) the need or urge to move the limbs, (2) characteristic symptoms that triggered by rest, relaxation, or sleep, 3) relief of symptoms with movement, and (4) symptoms that are worse at night and better in the morning. Laboratory testing may be performed, primarily to evaluate for some of the associated conditions. On occasion, special tests of nerve function or a sleep study is necessary to rule out other conditions

How is RLS treated? When a specific condition is responsible, the best way of treating RLS is to address that underlying problem. This may entail taking iron supplements in someone with iron deficiency anemia or blood sugar management in someone with diabetes. When the cause for RLS is unknown, there is no effective cure. There are treatments, however, aimed at reducing stress and helping muscles relax, which can help with the symptoms.

Lifestyle measures play an important role in alleviating symptoms associated with restless legs syndrome. The most important of these are:

• Avoidance of alcohol, caffeine, and nicotine - The use of tobacco products and the consumption of alcohol or caffeine-containing beverages is known to increase the intensity of RLS symptoms in many sufferers.
  
• Getting Regular exercise - Regular, moderate exercise often helps to relieve RLS symptoms. Exercising excessively, on the other hand, may intensify symptoms. Some sufferers find that light exercise or a stretching routine prior to bedtime is helpful in promoting sleep.
  
• Physical Therapy measures - These include gentle stretching exercises, massage, and taking a warm bath or applying hot packs to affected extremities.
  
• Establish a regular sleep routine - Irregular sleep habits may lead to sleep deprivation and aggravation of symptoms. Important "sleep hygiene" measures to promote restorative sleep include ensuring that the sleeping environment is comfortable and quiet, and going to bed and arising at the same time each day.

Medications are generally reserved for people with RLS who fail to find relief with lifestyle measures. Two medications with FDA approval for the treatment of RLS are pramipexole (Mirapex) and ropinirole (Requip). These are called "dopaminergic agents" because they increase a substance known as dopamine in the brain that is involved in nerve transmission. Other medications that may be used in treating RLS include: 1) carbidopa/levodopa (Sinemet), a drug more commonly used to treat Parkinson's disease, 2) clonazepam (Klonopin) and diazepam (Valium), used to help with sleep and muscle spasms and, 3) gabapentin (Neurontin) and pregabalin (Lyrica), anticonvulsants that can help decrease sensory disturbances such as the "creepy crawly" sensations. Opiate pain medications (Darvon, Tylenol #3, Vicodin, others) are sometimes given, but their addictive potential limits their long-term usefulness. It should be noted also that there are several medications that have been reported to make symptoms of RLS worse. These include OTC antihistamines, such as Benadryl, found in many cold or allergy medications, and anti-nausea medications, like meclizine and Phenergan.

What is the long-term outlook for someone with RLS? In most cases, RLS is a life-long condition that must be managed, rather than cured. This is similar to hypertension, in that it may not go away, but can be controlled. Through a combination of self-care measures and judicious use of medications, most people with RLS can find significant relief of symptoms.