Lung Cancer Overview and Causes

Lung Cancer

• Lung cancer is one of the most common and deadliest cancers globally, categorized into Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC).
• NSCLC accounts for about 85% of cases, with Adenocarcinoma (35-40%), Squamous cell carcinoma (30%), and Large-cell carcinoma (10%) as subtypes.
• SCLC accounts for about 15% of cases, is more aggressive, and responsible for 25% of lung cancer deaths due to early metastasis.

Most Likely Cause

• Smoking is the major cause, containing numerous carcinogens that modify genes, like the p53 tumor suppressor gene.
• Genetic mutations, such as oncogene activation (EGFR, KRAS) and loss of tumor suppressor genes, drive uncontrolled cell division.
• Occupational exposures (asbestos, arsenic, chromium, nickel, ionizing radiation) and air pollution (PM2.5) increase risk.
• Other factors such as family history and genetic predispositions also impact likelihood.

Pathophysiology

• Lung cancer development is complex, involving multiple mutations transforming normal epithelial cells into malignant ones.
• Oncogene activation (EGFR, KRAS) and loss of tumor suppressor genes (p53, RB1) are critical drivers of uncontrolled cell growth.
• Cancer cell growth is associated with evasion of apoptosis (cell death), leading to immortalization.

Types of Lung Cancer

• Squamous Cell Carcinoma: Starts in the central bronchi, grows slowly, and can cause airway obstruction (non-productive cough or hemoptysis).
• Adenocarcinoma: Originates in peripheral lung tissue, often linked to EGFR mutations (common in non-smokers), and tends to spread early.
• Large Cell Carcinoma: Composed of undifferentiated cells, arises centrally, progresses rapidly, and typically has a poor prognosis.
• Small Cell Lung Cancer (SCLC): Arises from neuroendocrine cells, spreads quickly, and often associated with paraneoplastic syndromes like SIADH (syndrome of inappropriate antidiuretic hormone) and Cushing's syndrome.

Disease Transmission

• Lung cancer is not contagious; it cannot be transmitted between people.
• Risk factors like secondhand smoke increase susceptibility, but transmission is not comparable to infectious diseases.

Risk Factors

• Modifiable: Smoking (leading cause, 80-90% of cases), secondhand smoke, occupational hazards (asbestos, arsenic, ionizing radiation), air pollution (PM2.5), and radon exposure.
• Non-modifiable: Age, genetic predisposition (mutations in p53, CYP1A1), and family history.

Clinical Features

• Symptoms depend on the type and stage: Cough (often persistent, non-productive), hemoptysis (coughing up blood), shortness of breath (dyspnea), weight loss.
• Paraneoplastic syndromes are seen with SCLC; these are diseases that occur due to lung cancer, such as SIADH and Cushing's syndrome, and the Eaton-Lambert syndrome.