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The prevalence of lung cancer among lifetime never-smokers is on the rise, but few people, including many physicians, recognize the risk in people with no history of cigarette smoking, a new commentary notes.

In the essay, titled "Lung Cancer in Never-smokers: a Hidden Disease," published in the , four public health officials in the U.K. called for increased awareness of lung cancer among lifetime never-smokers, with an emphasis on research to develop better screening methods for early detection in both smokers and non-smokers.

"From a public perspective, the historically strong and correct messaging on smoking and lung cancer had inadvertently contributed to lung cancer receiving much less press and political attention than many other cancers, such as breast, prostate, and ovarian cancers," the authors wrote.

The topic is intensely personal to the lead author, Prof. Paul Cosford, medical director of . A lifelong nonsmoker and fitness buff, Cosford was after being unable to complete a long-distance cycling competition due to his uncharacteristic shortness of breath and lack of energy.

A chest x-ray revealed pleural effusion, a collapsed left lung, and three liters of fluid in his pleural cavity. Further testing confirmed lung cancer in the left lower lobe and liver metastasis.

"For too long having lung cancer has only been thought of as a smoking-related disease," Cosford said in a press statement. "This remains an important association but, as this work shows, the scale of the challenge means there is a need to raise awareness with clinicians and policy makers of the other risk factors including indoor and outdoor air pollution."

Another co-author of the commentary, Michael D. Peake, MD, of the University of Leicester, told 乌鸦传媒 that the stigma associated with lung cancer, due to its close relationship with smoking, has greatly contributed to delayed diagnosis among nonsmokers.

Like Professor Cosford, most lifetime nonsmokers with lung cancer are diagnosed with advanced-stage disease, Peake noted. "We need much better tests for detecting lung cancer early than we have at the moment. By the time most [nonsmoking] patients are diagnosed, the disease is largely incurable. While lung cancer is not common among [lifetime] nonsmokers, it is not uncommon either, and physicians need to be aware that it occurs."

Peake said that in the U.K. alone, nearly 6,000 people who have never smoked die of lung cancer annually, which represents about 15% of total lung cancer fatalities.

The authors note that lung cancer in never-smokers is the eighth most common cause of cancer-related deaths in the U.K., with a greater mortality rate than lymphoma, leukemia, ovarian cancer, or cervical cancer.

"Globally, there is wide variation in the proportion of lung cancers in never-smokers, in the range of 10% to 25%," Peake, Cosford, and colleagues wrote. "With declining rates of smoking, the relative proportion of lung cancers in never-smokers are increasing and this does not appear to be confounded by passive smoking or misreported smoking status."

The authors noted that recent research describes "distinct clinical, pathological, and biological features of lung cancer in never-smokers." Research has documented that lung cancer in never-smokers is largely confined to non-small-cell lung cancers, "with a predominance of adenocarcinoma over squamous cell carcinoma of around 8:1 in Europe," they continued.

"Current estimates of the major contributors to lung cancers in never-smokers in the U.K. are: secondhand smoke (~15%), occupational carcinogen exposure (~20.5% men and 4.3% women), outdoor pollution (~8%), x-ray radiation (~0.8%), and radon exposure (~0.5%)," the commentary authors wrote.

They noted that women who have never smoked have a higher proportion of lung cancers than men who are lifelong never-smokers.

Genomics has had a dramatic impact on the understanding of differences between smoking-related and non-smoking related lung cancers, Peake, Cosford, and co-authors continued: "Never-smokers display distinct genotypes, with an increased prevalence of specific mutations, including EGFR, ALK-EML4, ROS-1, and BRAF, when compared to smokers."

The team explained that fewer mutations occur in lung cancers in never-smokers as compared with smoking-related lung cancer, but those that do occur are mostly involved in malignant transformation and are associated with better treatment-related prognosis. "The overall prognosis is improved in never-smokers compared to smokers, a finding which appears to reflect genotype rather than the effect of smoking itself," the authors stated.

They added that nonsmokers with lung cancer have half the rate of symptoms such as cough, dyspnea, and hemoptysis as patients who are current or former smokers.

The commentary authors argued that lung cancer among never-smokers should be considered as a differential diagnosis for these reasons.

Lifelong nonsmokers are not considered eligible for routine lung cancer screening under current screening guidelines. Peake said this makes sense given the significant limitations and risks associated with current screening practices.

"We need better screening methods for both smokers and non-smokers, and we need more research to make this a reality," he said.

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