Non-Smoking Lung Cancer May Be Different Disease

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While smoking is the single most significant cause of the majority of lung cancer cases in the United States, about 10 to 15 percent occur in people who have never smoked. New research finds that those non-smokers who develop lung cancer have a different disease, raising the possibility that the two groups should be treated differently.

Non-smoking Lung Cancer Patients Have More DNA Abnormalities

PhD Candidate Kelsie Thu and colleagues at the BC Center Research Center in Vancouver, Canada examined DNA of the tumors from 83 patients with lung cancer. Thirty of those never smoked, 14 were former smokers, and 39 were current smokers. Tissue samples of healthy cells were also taken from the patients.

While there were similarities, the lung tumors from nonsmokers had many genetic changes that were different from those found in smokers. For example, nonsmokers’ lung cancers had accumulated twice as many DNA abnormalities than the smokers’ tumors. And those who smoked more often carried one particular mutation (found in the epidermal growth factor receptor gene, or EGFR) and less often carried a KRAS mutation. EGFR mutations account for about 10% of lung cancers.

Interestingly, the tumors from former smokers more closely resembled those of nonsmokers than current smokers.

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In smokers, it is believed that the carcinogens in tobacco and cigarettes cause DNA mutations that lead to the uncontrolled growth of cancer cells. In nonsmokers, the genetic mutations suggest other molecular mechanisms at work.

"This is suggesting there might be something different going on with tumors in never-smokers," Thu said. "If we find out lung cancer in never-smokers is a different disease and we can identify what those differences are, maybe we can design specific therapies that target the genetic alterations in never-smokers and improve the prognosis."

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Lung cancer is the leading cause of cancer death in the US for men and women. Non-smoking lung cancer is more common in women than men. Asian women appear to be most particularly at risk. Nonsmokers also tend to be diagnosed at later, less curable stages because few suspect they have it.

Thu reported the findings in a presentation to the American Association for Cancer Research's Frontiers in Cancer Prevention Research Conference, held Nov. 7-10 in Philadelphia.

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