Why Do Some Smokers Never Get Lung Cancer, and Others Who Don’t Smoke End Up Getting It?

Cancer Q&A

By Joan Schiller, MD

Everyone knows that smoking is the major cause of lung cancer. In the early 1900s lung cancer was so rare that references to it were typically confined to the medical literature. Since then, the number of people who smoke has risen dramatically, as has the number of patients getting lung cancer, and the disease has become a national—even international—concern.

Epidemiological studies have shown that the more a patient smokes, the higher the risk of getting lung cancer, and that if they stop, the chances of getting lung cancer go down substantially (although not completely to zero). Still, not everyone who is a smoker will get lung disease. Why? Because our bodies are remarkably good at repairing themselves from injuries, and some people’s bodies are better at it than others’.

Joan Schiller, MD
Joan Schiller, MD
Professor and Chief, Hematology/Oncology

Many of the cancer-causing substances (carcinogens) found in cigarette smoke can injure the lung cells’ DNA, which is the equivalent of the “brains” of a cell. Abnormalities in the DNA (also known as mutations) will cause that cell to act abnormally. The more of these abnormalities or mutations that accumulate in the DNA of the cells, the more abnormally the cell behaves, until eventually the cell is able to grow, divide, replicate, and invade other tissues—the hallmarks of cancer.

So why don’t all smokers get lung cancer? Several reasons. First, one needs to accumulate a lot of these mutations before the cell becomes cancerous. Secondly, for reasons we do not completely understand, some people seem to be more susceptible to getting mutations from these cancer-causing substances than others. Finally, our bodies are remarkably good at repairing the mutations when they do happen, so in many cases they never cause the cell to become cancerous.

Nevertheless, some people will get enough mutations to cause cancer and their bodies will not be very good at repairing the abnormal cells’ DNA. About one in 10 smokers will get lung cancer, depending upon how much they have smoked. (About one in three smokers will die of a smoking-related illness—lung cancer, heart disease, emphysema, etc.)

So nonsmokers aren’t susceptible to lung cancer, right? Wrong. In fact, about 15% of lung cancers occur in people who have never smoked. In some people, exposure to other carcinogens in the environment, such as asbestos or radon, can lead to the disease.

Some individuals, however, have no known exposure to any known carcinogens. Scientists are just now beginning to learn about the mutation status in the DNA of nonsmokers and have found some unique mutations that are rarely, if ever, found in smokers. One such mutation is in a gene called the Epidermal Growth Factor Receptor (EGFR) gene. Although scientists do not know what causes this mutation, they have designed several drugs that are very effective in inhibiting it (erlotinib, or Tarceva, and gefitinib, or Iressa).

All in all, if you smoke, it is never too late to quit. Your risk of getting lung cancer decreases, as does your risk of dying from a smoking-related disease. At the same time, however, physicians and the public need to know that even a small number of people who have never smoked can get lung cancer, so if symptoms present themselves (persistent cough, shortness of breath), they should be evaluated with lung cancer as a possibility.