What Is The Pathophysiology of Lung Cancer?

Pathophysiology is the study of the functional changes that cause, result from, or are otherwise associated with the disease. In the case of lung cancer, the changes occur in the lungs. As the disease progresses, other areas of the body may be involved as well. 

This article will explore the causes of lung cancer, how it develops, and possible complications.

Types of Lung Cancer

The two main types of lung cancer are small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancers make up about 80% to 85% of all lung cancer cases and include:

• Adenocarcinomas begin in the cells that produce mucus.
• Squamous cell carcinomas begin in the squamous cells.
• Large cell lung carcinoma (LCLC) is named so because of its large, abnormal-looking cells. These cells can be found throughout the lungs but are typically located in the outer regions of the lungs.

Small cell lung cancers make up about 10% to 15% of all lung cancer cases and are sometimes called oat cell cancer. 

Causes

There are several possible causes of lung cancer. The leading cause of lung cancer is smoking tobacco. It’s estimated that about 80% of all lung cancer deaths are caused by smoking. Small cell lung cancer is almost always related to a history of smoking.

Other exposures that can lead to lung cancer are secondhand smoke, radon, air pollution, and asbestos. Some workplace exposures like diesel exhaust and other chemicals can also raise the risk of lung cancer. 

Inherited Gene Mutation

It’s possible to inherit a DNA mutation from one or both of your parents. It’s important to note that inherited mutations alone usually do not lead to cancer. They simply increase our risk. People who inherit a mutation in chromosome 6 are more likely to develop lung cancer even if they do not smoke tobacco. 

Other inherited mutations include people whose bodies cannot break down some of the chemicals found in cigarettes or who cannot repair damaged DNA.  

Some forms of non-small cell lung cancer cause the epidermal growth factor receptor (EGFR) gene to produce too much EGFR protein in the body. This is often seen in individuals with adenocarcinoma who do not have a history of smoking. 

Acquired Gene Mutation

While it is possible to inherit a gene mutation that can lead to cancer, most gene mutations are acquired over a lifetime. These mutations often occur due to environmental exposures and cause changes in the DNA of lung cells. These changes can then lead to abnormal cell growth and possibly cancer. 

DNA is a chemical in our cells that makes up our genes. We inherit DNA from both of our parents, and it can influence our risk of developing several chronic diseases, including cancer. The genes involved in cancer are:

• Oncogenes, which help cells to grow and divide.
• Tumor suppressor genes, which help control cell division and cause cells to die at the right time.

Gene mutations that may lead to lung cancer include:

• RB1 tumor suppressor gene: Small cell lung cancer
• p16 tumor suppressor gene: Non-small cell lung cancer
• K-RAS oncogene: Non-small cell lung cancer
• TP53 tumor suppression gene: Both small cell lung cancer and non-small cell lung cancer

Besides mutations, gene alterations—like translocations, for example—may also increase the risk of lung cancer. Examples of common translocations include:

• ALK gene: Non-small cell lung cancer
• Chromosome 3: Both small cell lung cancer and non-small cell lung cancer

Besides gene mutations and translocations, non-random chromosomal abnormalities associated with lung cancer have been described on chromosome 3 and chromosome 6.

Tobacco Smoke

Exposure to tobacco smoke is the leading risk factor for developing lung cancer. Smoking a cigar or pipe has been found to be almost as likely to cause lung cancer as cigarette smoking. 

Secondhand smoke can raise your risk of developing lung cancer. It’s estimated that secondhand smoke leads to 7,000 deaths from lung cancer each year. 

Radon

Radon is a naturally occurring radioactive gas that you cannot see, smell, or taste. It’s believed to be the second leading cause of lung cancer in people who do not smoke. Radon exposure usually happens inside the home. Breathing in small amounts every day raises your risk for lung cancer over time. 

Radon exists naturally in the soil and comes up into buildings through small cracks or gaps in the floor. It’s estimated that one in every 15 homes in the United States is at risk for radon exposure. If you’re unsure if your home is at risk, you can purchase a test kit from a hardware store to test the levels. 

Asbestos

Asbestos is a group of naturally occurring minerals that are likely found in mines, mills, textile plants, shipyards, and places where people work with insulation. Exposure to these minerals at work raises your risk for lung cancer, especially if you also smoke. 

Exposure to asbestos also raises your risk for mesothelioma, a type of cancer that starts in the lining surrounding the lungs, known as the pleura. Asbestos exposure usually occurs at work. Other workplace exposures that have been linked to lung cancer include:

• Uranium
• Arsenic
• Beryllium
• Cadmium
• Silica
• Vinyl chloride
• Nickel compounds
• Chromium compounds
• Coal products
• Mustard gas
• Chloromethyl ethers
• Diesel exhaust

History of Radiation to the Lungs

Receiving radiation to your chest is a risk factor for lung cancer, especially if you also smoke. People who may have a history of chest radiation include those treated for Hodgkin lymphoma or breast cancer. 

Air Pollution

It’s estimated that air pollution is to blame for about 5% of all lung cancer deaths worldwide. This risk factor is difficult to address because we as individuals usually do not have control over the quality of the air we breathe. 

History of Lung Cancer

Having a personal or family history of lung cancer raises your risk of developing the disease. Talk with your doctor if lung cancer runs in your family, especially if you experience other risk factors. 

Cancer research is constantly evolving, and we may learn of additional causes in the future. The following substances may raise your risk for lung cancer, but there is not yet enough evidence to be sure:

• Smoking marijuana
• E-cigarettes
• Talc and talcum powder

Symptoms of Lung Cancer

Lung cancer does not always cause symptoms in the early stages. Often, symptoms present once cancer has begun to spread. As soon as you develop any signs or symptoms of lung cancer, it’s important to see your doctor right away. 

The most common signs and symptoms of lung cancer include:

• A persistent cough
• Coughing up blood or blood-tinged sputum
• Chest pain
• Loss of appetite
• Unintended weight loss
• Shortness of breath
• Fatigue 
• Respiratory infections that don’t improve
• New-onset wheezing 

Summary

The pathophysiology of lung cancer refers to the physical changes happening in the body that lead to lung cancer. The leading cause of lung cancer is exposure to tobacco smoke. Other possible causes include radon, asbestos, radiation, and air pollution. Gene mutations, either inherited or acquired, may raise your risk of developing lung cancer. Signs and symptoms include a persistent cough, coughing up blood, chest pain, and loss of appetite. 

A Word From Verywell 

Dealing with a cancer diagnosis is incredibly stressful. It may feel helpful to better understand which factors affected your risk of cancer, as well as signs to watch for. Lung cancer is most often caused by exposure to tobacco smoke. If you or a loved one need help to quit smoking, talk with your doctor about resources in your area.