What is small-cell lung cancer?

Risk Factors

Smoking is the greatest risk factor for SCLC, with an estimated 87 percent of lung cancers caused by smoking. Other risk factors are exposure to radon, asbestos, beryllium, cadmium, silica, vinyl chloride, nickel- or chromium-containing compounds, coal products, mustard gas, chloromethyl esters, diesel exhaust, radiation to the chest, arsenic, air pollution, radioactive substances like uranium, and genetic factors.

Etiology and Genetics

The National Cancer Institute estimates that more than 224,000 new lung cancer cases and 159,260 deaths will occur in 2014, with SCLC accounting for about 15 percent of these. Cancer in general is considered to be a genetic disease because cancer is associated with genetic changes in somatic cells that lead to uncontrolled cell growth. Lung cancer is not caused by a single gene. The human genome is made up of pairs of chromosomes. When tissue from the lungs of smokers is genetically analyzed, several areas of the DNA that makes up chromosomes and contain the genes are found to be damaged, duplicated, or missing. However, not all smokers with genetic damage in their lung tissue have lung cancer, suggesting that multiple sites of DNA damage must accumulate before lung cancer develops. Not every SCLC case has the same set of mutated genes present, but damage to specific regions on chromosomes 1, 3, 4, 5, 8, 9, 10, 11, 13, 15, 16, 17, 18, and 20 occurs frequently in SCLCs. In SCLC and other cancers, one of the most commonly mutated genes is called p53, a gene that usually causes damaged cells to undergo programmed cell death, known as apoptosis. When the p53 gene is mutated, the damaged cells do not die and can go on to become malignant cells.

While 85 percent of all lung cancers occur in former or current smokers, fewer than 20 percent of long-term smokers develop lung cancer, suggesting that genetic factors make some people more susceptible to lung cancer. In 2009, researchers identified two sites of genetic variation on chromosome 15 that people can inherit from their parents that are associated with an increased risk of lung cancer in smokers and former smokers. These genetic variations, called single nucleotide polymorphisms (SNPs), are places in the human genome that vary by a single DNA nucleotide. People who have one or two copies of either of these SNPs and who have ever smoked have increased risks of 28 percent to 81 percent of developing lung cancer. The two SNPs identified are near five genes on chromosome 15. Interestingly, three of these five genes encode proteins that serve as docking sites for nicotine, the addictive agent in tobacco. These findings suggest that nicotine, in addition to several known carcinogens present in tobacco smoke, may be involved in lung cancer development. Another of the genes near the SNPs encodes a component of the proteasome, an important organelle in cells that degrades other proteins. The function of the fifth gene is unknown.

Symptoms

In early-stage SCLC, patients often do not have symptoms. Symptoms of lung cancer include a cough that does not go away; chest pain that often gets worse with deep breathing, coughing, or laughing; hoarseness; unexplained weight loss or lack of appetite; bloody or rust-colored spit or phlegm (also called sputum); shortness of breath; recurrent infections like bronchitis and pneumonia; and new onset of wheezing. Small-cell lung cancer commonly spreads or metastasizes to other organs. Symptoms of cancer that has spread include bone pain; weakness or numbness in the limbs; headache, dizziness, or seizure; jaundice; and lumps near the surface of the body such as lymph nodes in the neck. Those who experience these symptoms should see a physician right away.

Screening and Diagnosis

Chest x-rays and checking sputum under a microscope to look for cancer cells was studied as a screening tool for lung cancer for several years. Unfortunately, this kind of screening is not very effective, with very few lung cancers found early enough to improve a person’s chances for a cure. Because this kind of screening is not very effective, it is not done routinely, even in smokers who are at high risk. However, a newer screening method, spiral computed tomography (CT) scanning, was tested in the National Lung Screening Trial from 2002 to 2010 and found more effective than chest x-rays at detecting cancer, and since 2013, medical authorities have recommended this form of screening for high-risk individuals.

Treatment and Therapy

Small-cell lung cancer has usually spread or metastasized to other organs before it is diagnosed; therefore, it is usually not treated with surgery. Patients with advanced-stage disease are usually treated with platinum-based chemotherapy (cisplatin or carboplatin), which may be combined with the drugs etoposide or camptothecin-11. Patients whose tumors respond very well to chemotherapy may also be offered radiation therapy.

Prevention and Outcomes

The most important prevention for SCLC is to not smoke, or to quit smoking. After quitting smoking, it takes about ten years to reduce the risk of lung cancer in former smokers, but the risk never drops to the level of those who never smoked.

Bibliography

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