From the Grace Archives | Originally Published November 12, 2014 | By Dr. Weiss

Smoking is the most common cause of lung cancer; 85% of lung cancer patients have smoked at some point in their lives (or, stated another way, 15% of lung cancer patients have never smoked).  While quitting smoking certainly decreases the risk of getting lung cancer, more than half of lung cancer happens in people who have quit. 

Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report, “Cigarette Smoking Among Adults – United States, 2006”, November 9,2007/56(44): 1157-1161, Table 2

Reason #1 to not blame the lung cancer patient:

He or she may have never smoked.  I just visited a very young patient of mine while he was dying at home of lung cancer.  He never smoked.

Reason #2 to not blame the lung cancer patient:

The smoking may not have caused the cancer.

Smoking is not the only cause of lung cancer.  Other causes include occupational carcinogen exposure, radon, and outdoor air pollution.  There are probably other, as yet undiscovered, causes. 

I’ll add a cause that is rarely directly discussed: an (un)healthy dose of bad luck. The majority of active smokers and former smokers do not get lung cancer.  Cigarette smoke contains numerous chemicals that can cause mutations, or changes in the DNA of cells. Some DNA codes for important proteins—mutations to these areas of DNA have the potential to cause cancer.  Other parts of DNA are “junk” that don’t actually code for anything.  While there is active research into why some people get cancer from cigarette smoking and others don’t, the luck of having these mutations in “junk” regions or in important ones surely plays a major role. 

Dr. Jared Weiss (Courtesy of UNC Lineberger)

Smokers and nonsmokers have similar chances of developing smoking-unrelated lung cancer. Scientists now believe that non-smoking related lung cancers tend to be biologically simpler—they have one or two “driving” mutations that transform a healthy lung cell into a lung cancer cell (for example, EGFR or EML4/ALK).  In contrast, smoking-related cancers may have more mutations that together contribute to transforming that healthy lung cell into a cancerous one.  But, there is absolutely nothing about smoking, even heavy smoking, that protects a person against a smoking-unrelated lung cancer.

This last point is important not only for how we think or feel about people with lung cancer, it also has a very important practical consequence for medical practice. All patients with metastatic non-squamous non-small cell lung cancer (the type that might have mutations that can be treated with targeted therapies such as erlotinib or crizotinib) deserve molecular testing, regardless of how much they smoked. 

In my practice, I have found several patients with EGFR mutation (treatable with erlotinib or afatinib) and at least 1 with EML4/ALK (treatable with crizotinib) amongst patients with a smoking history.  Statistically, patients who have smoked a lot may have a lower probability of having such mutations, but there is still a real chance, and I feel strongly that these patients deserve testing.