What percentage of patients without a smoking history develop primary lung cancer?

Percentage of Patients Without Smoking History Who Develop Primary Lung Cancer

Approximately 10-25% of all primary lung cancer cases occur in patients who have never smoked. 1, 2

Epidemiological Characteristics of Lung Cancer in Never-Smokers

Global and Regional Variations

• In the United States, lung cancer in never-smokers represents approximately:
  • 19% of cases in females
  • 9% of cases in males 3
• In Sweden, a large population-based cohort study found that 11% of non-small cell lung cancer (NSCLC) patients had never smoked 4
• Higher prevalence is observed in Asian countries, particularly in South-East Asia 2
• In China, there has been an increase in the proportion of NSCLC patients who are never smokers 3
• In Korea, the proportion of lung cancer cases in never smokers increased from 19.4% (2004-2008) to 25.4% (2009-2012) 3

Gender Distribution

• Never-smokers with lung cancer are more frequently women across all geographical locations 2
• Women are over-represented among younger patients with lung cancer, suggesting gender-specific differences in susceptibility to lung carcinogens 3
• In a Swedish population-based study, never-smokers with NSCLC were more often women and older compared to ever-smokers 4

Clinical and Pathological Characteristics

Histological Subtypes

• Adenocarcinoma is the predominant histological subtype in never-smokers:
  • 77% of lung cancers in never-smokers vs. 52% in current smokers and 57% in former smokers 4
• Squamous cell carcinoma is less common in never-smokers compared to smokers 2

Disease Stage at Diagnosis

• Stage IV disease is more common in never-smokers (57%) compared to current (48%) and former smokers (48%) 4

Molecular Profile

• Distinct molecular characteristics in never-smokers:
  • Higher prevalence of EGFR mutations: 37% in never-smokers vs. 5% in current smokers and 9% in former smokers 4
  • ALK rearrangements are more common in never-smokers 2
  • Lower frequency of KRAS mutations compared to smokers 3

Risk Factors for Lung Cancer in Never-Smokers

Environmental Factors

• Second-hand smoke exposure (environmental tobacco smoke) 3
• Radon exposure (residential and occupational) 3
• Occupational exposure to carcinogens (arsenic, chromium, asbestos, nickel, cadmium, beryllium, silica, diesel fumes) 3
• Air pollution (indoor and outdoor) 3
  • Indoor air pollution from cooking oil fumes and coal-fueled stoves 3
  • In China, inadequate ventilation in kitchens increased lung cancer risk in never-smoking females (HR 1.49) 3

Genetic and Family History

• First-degree relatives with lung cancer have an RR of 1.8 (95% CI, 1.6-2.0) for developing lung cancer 3
• The risk is greater in individuals with multiple affected family members or those diagnosed at a young age 3
• Genetic susceptibility loci have been identified that may increase lung cancer risk 3

Medical History

• History of lung diseases, particularly COPD and pulmonary fibrosis 3
• COPD accounts for 10% of lung cancer cases among never-smokers 3
• Patients with diffuse pulmonary fibrosis have a higher risk for lung cancer (RR 8.25) 3
• Previous history of cancer, especially those treated with radiation therapy or alkylating agents 3

Prognosis and Treatment Implications

• Both lung cancer-specific and overall survival are higher for never-smokers compared to current smokers 4
• EGFR-tyrosine kinase inhibitors (erlotinib and gefitinib) are more effective in never-smokers due to higher incidence of EGFR mutations 2
• Never-smokers with lung cancer should be tested for actionable mutations, particularly EGFR 3

Clinical Implications

• The distinct epidemiological, clinical, and molecular characteristics of lung cancer in never-smokers suggest it should be considered a separate disease entity 5
• Screening and early detection strategies may need to be tailored differently for never-smokers
• Molecular testing is crucial in never-smokers to identify actionable mutations for targeted therapy
• Understanding the pathogenesis of lung cancer in never-smokers is essential for developing prevention strategies and novel therapeutic approaches

Despite the growing body of information on lung cancer in never-smokers, further research is needed to better understand its pathogenesis, improve early detection, and develop more effective treatment strategies for this distinct disease entity.