Patient Education

Lung cancer can occur in non-smokers. The population trend in lung cancer is changing, and this is increasingly recognised worldwide. In Asia, up to a third of lung cancer patients diagnosed are never smokers, while the figures in the West are a much lower 10 to 20%. The numbers are startingly higher in Singapore, with a 2018 study by the National Cancer Centre Singapore (NCCS) reporting that almost half of lung cancer patients were non-smokers who have never smoked before. Intriguingly, there are differences between genders too. In one of the studies reported, approximately 15% of men compared with 60 to 80% of women with lung cancer were non-smokers!

Causes of Lung Cancer in Non-Smokers

While it's widely believed that smoking is a large contributing factor to lung cancer, non-smokers are not exempt from the disease. But what about non-smokers? How do they develop lung cancer? Various environmental and genetic factors may contribute to the onset of lung cancer in those who have never smoked. Some possible causes include:

• Radon exposure: A natural radioactive gas found in many homes, radon is the second leading cause of lung cancer.
• Secondhand smoke: Living with a smoker can increase a non-smoker’s risk of developing lung cancer.
• Workplace exposure: Substances like asbestos, arsenic, diesel exhaust, and certain chemicals used in manufacturing can significantly elevate cancer risk.
• Pollution: Extended exposure to air pollution, especially in heavily industrialised parts of Singapore with poor air quality.
• Genetic predisposition: Some individuals inherit DNA mutations that greatly increase their risk of lung cancer.

Does Vaping Cause Lung Cancer?

The rise of e-cigarettes and vaping has emerged as a new concern for lung health, particularly in Singapore. With the number of known vape possession cases reaching a new high of 7,900 in 2023, it's crucial to understand the potential risks associated with vaping.

While research on the long-term effects of vaping is still ongoing, some concerning correlations have emerged. E-cigarettes and vape liquids contain various chemicals, some of which are known carcinogens (cancer-causing agents) like benzene and formaldehyde. These chemicals, along with ultrafine particles inhaled through vaping, can irritate and damage lung tissue.

It's important to note that a definitive link between vaping and lung cancer has not yet been established. However, the presence of harmful chemicals and the potential for lung damage raise significant concerns.

Can Haze Cause Lung Cancer?

It comes as no surprise that environmental factors such as air pollution, including haze and smog, can contribute to the development of lung cancer. These pollutants can initiate or accelerate damage to lung cells.

With the regional haze affecting countries in Asia like Singapore, Malaysia, Indonesia and Brunei, some patients have asked about the effect of haze on lung cancer. Haze is known to carry small PM 2.5 particles that can penetrate deeper into the bronchi (or lung airways). Fine particulate matter less than 2.5 microns (PM2.5) is an air pollutant that affects people's health and reduces visibility outdoors.

Besides causing a host of health problems affecting the respiratory tract and eyes, studies suggest that long-term exposure may be associated with increased mortality from lung cancer and heart disease. People with chronic lung and heart problems, childrenm and the elderly may be particularly sensitive to PM2.5.

How Rare is Lung Cancer Among Non-Smokers?

Our oncology specialist, Dr Leong Swan Swan, is one of the co-authors of a publication in 2006 (Journal of Clinical Oncology) of never smokers with non-small cell lung cancer (NSCLC) in Singapore. Out of 883 patients, 68.5% of the non-smokers in their study with non-small cell lung cancer were females. The median age at diagnosis for lung cancer in patients who have never smoked was younger than that for current / ex-smokers.

Can Genetics Influence Lung Cancer Risk in Non-Smokers?

The question of whether genetic susceptibility plays a part is suggested mainly by population-based studies, where some studies have shown an association between lung cancer in non-smokers and a family history of lung cancer. The difficulty is teasing out environmental exposures in these studies with an appropriate control group. With modern DNA technology using genome-wide association studies (GWAS), results have been mixed.

The epidermal growth factor receptor (EGFR) is an important gene belonging to the tyrosine kinase family. In non-small cell lung cancer, EGFR mutation is known to be more common in the tumours of never-smokers compared to smokers. Interestingly, some of these mentioned families have germline mutation in the epidermal growth factor receptor which increases their risk for lung cancer. There have been other genes including HER2, reported in these families. There was also a reported mutation in EGFR in T790M, a mutation which confers drug resistance.

Different Biological Types Of Lung Cancer

Many people might consider lung cancer as a single disease, but increasingly this is changing. Among smokers, the most prominent variations of lung cancer involve the following:

• Small Cell Lung Cancer (SCLC): SCLC is highly associated with smoking and known for its rapid growth and early spread to other organs. It often starts in the bronchi and is very aggressive, responding differently to treatments compared to other types.
• Squamous Cell Carcinoma: This type of lung cancer is strongly linked to smoking. It usually occurs in the central part of the lungs near the bronchus and is characterised by cells that are flat and scale-like in appearance. It tends to be more localised than other types.
• Large Cell (Undifferentiated) Carcinoma: This cancer can appear in any part of the lung and tends to grow and spread quickly, which makes it more difficult to treat. It is less directly associated with smoking compared to SCLC and squamous cell carcinoma but still more common among smokers than non-smokers.

What Kind of Lung Cancer Do Non-Smokers Get?

The predominant cell type in non-smokers with lung cancer is adenocarcinoma. In contrast, lung cancer which develops in smokers, although frequently also of adenocarcinoma cell type, has a higher proportion of squamous cell and small cell subtypes.

On a molecular basis, there are clear differences in these lung cancers. These differences are not appreciated by just examining the tumour under a microscope or immunohistochemistry. Typical variations of lung cancer among non-smokers would include:

• Adenocarcinoma: Most common among non-smokers, adenocarcinoma generally grows in the outer regions of the lungs and may develop from pre-existing conditions like atypical adenomatous hyperplasia. It is slower growing and responds differently to treatments compared to other types.
• Bronchioloalveolar Carcinoma: A subtype of adenocarcinoma, it is less aggressive and tends to be localised to one area of the lung. Known for its unique growth pattern along the pre-existing structures of the lung without invading surrounding tissues.
• EGFR Mutated Lung Cancer: Not a distinct type per se, but common in non-smokers. Tumors with Epidermal Growth Factor Receptor (EGFR) mutations are particularly responsive to targeted therapy, which is less toxic than traditional chemotherapy.
• ALK-Rearranged Lung Cancer: Characterised by the rearrangement of the ALK gene, creating an abnormal ALK protein that contributes to cancer development. More common in non-smokers and has effective treatment options with ALK inhibitors.
• ROS1-Rearranged Lung Cancer: This type involves changes in the ROS1 gene leading to fusion with other genes, resulting in cancer-promoting proteins. These tumours are rare but tend to occur in younger and non-smoking individuals and are highly sensitive to targeted treatments similar to those used for ALK rearrangements.

Molecular analysis with techniques for mutation in specific genes, and probes for fusion genes are needed. At OncoCare Cancer Centre, Singapore, we have access to good-quality laboratories that perform these tests with a reasonable turnaround time. Some of these molecular mutations tested are EGFR, ALK Rearrangement, and the ROS-1 Gene.

Symptoms of Lung Cancer

Be it a smoker or non-smoker, the symptoms of lung cancer tend to be similar across different types and variations. Some of the common symptoms associated with lung cancer include:

• Persistent Cough: A new cough that doesn’t go away or changes in a chronic cough.
• Coughing Up Blood: The presence of blood in sputum, even in small amounts.
• Chest Pain: Pain that may be worse with deep breathing, coughing, or laughing.
• Shortness of Breath: Difficulty breathing, which can be due to blockages or fluid accumulation.
• Unexplained Wheezing: Wheezing that occurs without any known cause like asthma.
• Hoarseness: Changes in voice or hoarseness that persist.
• Unexplained Weight Loss: Losing weight without changes to diet or exercise routines.
• Loss of Appetite: A decreased desire to eat.
• Fatigue: Excessive tiredness not relieved by rest.
• Recurrent Respiratory Infections: Infections such as bronchitis or pneumonia that recur or do not resolve.
• Swelling of the Neck and Face: This can occur if the tumour presses on the vein that runs from the head to the heart (superior vena cava obstruction).

Treatment Of Lung Cancer In Non-Smokers

Can we cure lung cancer in non-smokers? if detected early, the chances of remission are much higher. Unfortunately, fewer patients with early stage I and stage II lung cancer are diagnosed. Unlike locally advanced and disseminated (stage IV) lung cancer, early lung cancer can be treated with curative intent with aggressive management. In some of these patients with early-stage lung cancer, adjuvant chemotherapy or chemo-radiotherapy may further improve survival as well.

The advantage for non-smokers in contrast to smokers is that generally, their lung condition is healthier (better pulmonary function). This allows them to tolerate aggressive treatment like resection of part of the lung (e.g., lobectomy, pneumonectomy) better. On the other hand, non-smokers may not suspect that they will ever get lung cancer and diagnosis of lung cancer may be delayed and detected at a more advanced stage, if the suspicion is not high for example, for a persistent cough.

Specific drugs or medications used in never-smokers compared with smokers has been best studied in tumours with EGFR mutations. Higher response rates have been reported for EGFR tyrosine kinase inhibitors (TKI) as compared to chemotherapy if the patients have an EGFR mutation. These oral drugs like Erlotinib (Tarceva), Gefitinib (Iressa), and Afatanib (Giotrif) have transformed lung cancer treatment, improving outcomes and tolerability with good quality of life. Similar advances have been made with targeted agents against ALK and ROS-1, like Crizotinib and Ceritinib.

At OncoCare, you have access to leading cancer specialists in Singapore who offer a comprehensive suite of treatments and diagnostic services tailored to your specific needs. Whether you are exploring initial symptoms or seeking therapy, we are here to support your journey. Learn more about the different types of cancer in our patient education blogs, or sign up for a clinical trial today to explore treatment options.

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