Lung Cancer: Causes, Screening and Tools for Diagnosis

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Lung cancer is the most common cancer in the world. In 2012, 1.8 million new cases were diagnosed. Yearly, there are an almost equal number of deaths from lung cancer. In the United States, 225,000 new cases are diagnosed annually, and there are 160,000 fatalities a year due to this cancer.

Cases of lung cancer have grown steadily over the past several decades. In 1958, lung cancer was the most common cause of cancer death in men. By 1985, it was the most common cause of death among women, reflecting the delayed “catch up” that reflected increasing numbers of women smoking as a regular habit. In recent years, lung cancer deaths have showed some decline in the U.S. (but not yet globally), reflecting a decline in rates of smoking and also more effective treatments for lung cancer.

Risk factors that contribute to lung cancer have been studied extensively. Smoking is still the clear front runner, associated with over 90 percent of lung cancer cases. Still, growing attention is now being paid to cases of lung cancer in non-smokers, and there has been an accelerated effort to identify other factors that are contributing to lung cancer rates, especially in women.

Some of those identified factors include:

  • Radiation therapy received as treatment for other malignancies
  • Environmental toxins: Exposure to second-hand smoke, occupational exposure to asbestos and metals including chromium, arsenic and polycyclic aromatic hydrocarbons. The International Agency for Research on Cancer (IARC) has a classification for many substances that have carcinogenic potential.
  • Other medical conditions that increase the tendency for malignant transformation in the lung. Some examples include pulmonary fibrosis, HIV, and inflammatory conditions such as ulcerative colitis and polymyositis.
  • Genetic factors: This is determined by familial history and the implications are also used to determine the response to specific therapy.
  • Dietary factors: Some substances such as phytoestrogens (soy) and cruciferous vegetables have been shown to reduce the risk of lung cancer, but in one study that looked at beta-carotene, results showed an increase of cancer in smokers who used this supplement. More research on dietary factors is needed.
  • Radon exposure: This is a radioactive isotope of uranium that persists as remnants in the ground soil.

What are the best strategies when screening for lung cancer?

The accumulated knowledge we now have of the variety of risk factors has helped to drive more opportunities to identify high-risk individuals who should undergo early intervention to mitigate some of these risk factors. Finding these individuals for early and robust screening of lung cancer is important.

Doing regular chest x-rays on individuals who smoke is something that has made sense. In fact, if a smoker is diagnosed with lung cancer and did not undergo routine chest x-rays, their doctor could be subject to a malpractice lawsuit. The truth is that long term studies have failed to demonstrate that “yearly chest x-rays on smokers reduced mortality.” Since reducing mortality is the end goal, the U.S. Preventive Services Task Force now recommends against excessive use of chest x-rays as a screening measure. The protocol is to consider use of chest x-ray screening on an individual basis.

The recent National Lung Screening Trial that used low radiation CT scanners showed that using this tool for screening resulted in lower mortality rates. Medicare now pays for CT scans on asymptomatic patients who have risk factors. There are however a number of restrictions on the use of this screening tool. For example, a former smoker who quit smoking over 15 years ago is not considered a candidate for a CT scan, although this person may rightfully believe that he is not risk free and should have coverage for this type of screening. Patients under these circumstances would have to pay out-of-pocket.

The importance of screening rests in the fact that by the time a tumor is discovered, there will likely have been a large generation of cells that have already divided and spread. There are now screening blood tests that can identify early stages of some cancers (prostate and ovarian cancer). There are no current blood screening tests for lung cancer, however.

Lung cancer typically starts with a normal cell that has proteins involved in regulating cell division and death, allowing for an orderly transition from old cells to new. When this orderly regulation is disrupted or lost, cells divide at a faster rate. This is important because it means that anything that can alter the structure of these proteins, such as oxidative stress, will prompt the process that further alters the structure and function of these proteins, and will likely instigate cancer.

The proteins that allow unrestricted cell growth are called oncogenes. They stimulate cell growth without being controlled by proteins that would normally suppress that growth. It’s like driving a car, stepping on the gas -- and the accelerator gets stuck. The car continues to speed up regardless of the driver’s desire. It’s an out-of-control situation.

The most frequently mentioned oncogene in lung cancer is called the KRAS mutation which is responsible for 10-30 percent of all adenocarcinomas.

The process starts insidiously. First there are areas of pre-cancerous cells that show the early changes in the proteins but are not affected by the irregular growth. As these cells change and mutate with further cell division, they produce chemicals that cause the growth of more blood vessels. These blood vessels nourish the process and they eventually become cancer cells. Even then, it will take many divisions and growth cycles (months) until the growing tumor (nodule) blocks one of the small airways and can be visualized on a chest x-ray.

Next: Diagnosis and Classification of Lung Cancer

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