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Lung Cancer: Types and Causes

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Lung cancer accounts for 14.1% of newly diagnosed cancers and 20% of cancer deaths worldwide. 59% of the world’s lung cancer cases occur in Asia. This cancer is the number one cause of cancer deaths in men and the second leading cause of cancer deaths in women. Epidemiological studies also reveal that those who have never smoked make up one-third of all lung cancer patients in East Asia.  

In another article, we have discussed the risk factors, diagnosis and treatments of lung cancer. What about the causes and different types? Continue reading to find out more.

Aetiology 

Genetic predisposition

The risk is higher in individuals with a first-degree relative (e.g. parent, sibling, or child) with lung cancer

Genetic abnormalities

Stepwise accumulation of genetic abnormalities that transform bronchial epithelium to cancerous tissue 

Industrial hazards

These include high-dose ionising radiation or asbestos which can act alone or together with cigarette smoking

Infections

Viral infections such as HPV6 and HPV11 in laryngeal papillomatosis (a rare condition benign tumours form along the respiratory tract and the upper part of the digestive tract) 

Lung injury

  • Chronic obstructive pulmonary disease (COPD): A chronic inflammatory lung disease that causes obstructed airflow to the lungs
  • Alpha-1-antitrypsin deficiency carriers: A disorder that affects 1 in 2000 individuals with European ancestry. However, it is uncommon among Asians.
  • Idiopathic pulmonary fibrosis: Occurs when the lungs become scarred and breathing becomes increasingly difficult

Passive smoking and secondhand smoke

By being around someone who smokes in the house, your risk of lung cancer increases by 1.1 – 3.4 times. Women are also more vulnerable than men, making up as much as 70% of never-smokers with lung cancer in Singapore.

Passive smoking during childhood is also associated with a higher chance of developing nasal cancer. This is mainly due to the carcinogenic components in cigarettes, including aromatic hydrocarbons and nitrosamine, which result in DNA damage. 

Smoking 

Tobacco smoking is the single most important preventable risk factor with 80% of lung cancer cases attributable to tobacco smoking. Smoking is most strongly related to squamous cell carcinoma and small cell carcinoma. There is a typical delay of 25-30 years between smoking and the diagnosis of lung cancer. Studies have shown that never-smokers who develop lung cancer have a higher survival rate than those who smoke.  

Symptoms and signs

  • Presenting complaints: cough, weight loss, chest pain, difficulty breathing (dyspnoea), coughing out blood
  • Other less common signs: pneumonia, pleural effusion, Pancoast syndrome, paraneoplastic syndrome, metastatic diseases

Diagnostic Modalities

  • Imaging: Chest X-ray, CT Scan, PET scan for staging studies
  • Non-invasive: Sputum cytology
  • Invasive: Fine needle aspiration of primary lesion of metastatic disease, image-guided core biopsy, thoracoscopic biopsy 

Types of lung cancer 

Lung cancer is usually characterised as two main types based on the microscopic examination of a lung biopsy: non-small cell lung cancer and small cell lung cancer. 

Non-small cell carcinoma accounts for 80% of patients and grows more slowly than small cell lung cancer. This type of cancer is more limited to the lungs and patients have a higher survival rate than patients with small cell lung cancer. 

On the other hand, small cell lung cancer grows rapidly and spreads (metastasises) to other organs earlier than NSCLC and is found mostly in smokers. 

Non-small cell lung carcinoma (NSCLC) 

Typically, 70% of patients are diagnosed when they present with advanced stage characteristics. This means that the cancer has spread to either the tissues surrounding the lungs or to another part of the body (metastatic disease). 

Half of NSCLC are caused by point mutations and other biomarkers. Point mutations are single base changes in the genome that may result in gene augmentations that change protein expression, affecting the body significantly. 

Biomarkers differ greatly depending on ethnicity. The proportion of EGFR mutations is much higher in Asia than that of patients in Western countries. EGFR is a protein found on the surface of some cells that help with growth, but mutations lead to uncontrollable tumour manifestations.  

There are many different genetic mutations in non-small cell lung cancer. Cancers in never-smokers are more likely to have EGFR mutations, KRAS mutations and ALK rearrangements. These tend to occur in the peripheral lung and are associated with fibrous scarring and pleural retraction.  

Adenocarcinoma

Adenocarcinoma is a malignant tumour with glandular differentiation or mucin production by tumour cells and occurs in smokers and non-smokers. It is the most common type of lung cancer in women. The five-year survival rate varies from 69% in Stage I to 8% in Stage IV. 

Squamous Cell Carcinoma 

Squamous cell carcinoma is strongly associated with smoking and is characterised by squamous differentiation on histology. It usually arises centrally in the lung, obstructing the left or right main bronchus. 

Lung Cancer Treatment 

Surgery is performed in 20-30% of cases for Stages 1 and 2 in non-small lung carcinoma. Chemotherapy is administered to lower the risk of relapse and increase survival rates. Other targeted treatments such as radiotherapy are used when the cancer has metastasised, as seen in Stage 4 cancer patients.

Small cell carcinoma arises centrally, with widespread involvement of the lung. The cancer is usually metastatic, and chemotherapy is the first line of treatment for these cases. 

Over the years, targeted drugs and immunotherapy have been developed, with the discovery of specific genetic mutations. These modalities have prolonged survival rates as compared to chemotherapy, but treatment is very costly. 

Conclusion

Research has shown that prevention is better than cure and non-smokers are encouraged to better protect themselves by refraining from smoking and avoiding long hours of exposure to smoke. 

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