Never Smoke?: The Hidden Genetic Drivers of Lung Cancer

These days, lung cancer is no longer just a smoker’s disease. You might have heard that smoking is the main cause of lung cancer — and while that’s still true, recent research and clinical experience reveal a rising trend: people who have never touched a cigarette, especially women, Asians, and younger individuals, are being diagnosed with lung cancer at a significantly higher rate.

So, what’s really behind this? The secret isn’t out there. It’s in you.
 

When you don’t smoke… but still get lung cancer

Beyond tobacco, there are many other factors that can raise your risk:

• Secondhand smoke, especially from early childhood exposure
• Air pollution (PM2.5), which can trigger EGFR gene mutations
• Radon gas from soil or older buildings
• Cooking fumes, particularly from reused oil or charcoal stoves
• Occupational toxins like asbestos or arsenic
• Chronic lung disease or prior radiation therapy
• Estrogen, which may play a role in some women

But among all these, genetics may be the most important — especially if there’s a history of cancer in your family or if cancer appears at a young age.
 

Did you know? Lung cancer in non-smokers is often a different type

In non-smokers, lung cancer is most often non-small cell lung cancer (NSCLC) — particularly adenocarcinoma — accounting for more than half of all cases.
By contrast, small cell lung cancer, which is closely linked to smoking, is rarely found in non-smokers.

This striking difference suggests that…
The “root cause” in non-smokers may not come from environmental triggers, but from internal mechanisms — hidden genetic mutations present from birth.
 

Breaking news from the medical field: Genetics as the missing link

A groundbreaking study from Japan (published June 2025) found that:

• Asian women and younger individuals (<50 years) who have never smoked face a higher risk of lung cancer than other groups

• Commonly detected genetic mutations include:

  • TP53 – a key tumor-suppressor gene, linked to Li-Fraumeni syndrome and adenocarcinoma

  • BRCA2 – previously known for breast and ovarian cancers, now also implicated in early-onset lung cancer

  • ALKBH2 – crucial for DNA repair, especially after exposure to carcinogens

Even more striking:
These mutations were found not only in cancer cells but also in normal body tissues — known as germline variants — meaning they were present from birth.
This is different from somatic mutations, which develop later due to external triggers like smoke or pollution.
In simple terms: For some people, cancer may start “from within,” not from the environment. And that’s exactly why genetic testing before symptoms appear could save lives.
 

Genetic testing = Seeing risk before disease strikes

There are two main types of genetic testing, each serving a different purpose:
Germline DNA testing

• Looks at DNA inherited from your parents — present in every cell since birth
• If certain genes carry mutations, you may be predisposed to specific diseases, even if you’re healthy now
• Ideal for prevention — e.g., identifying lung cancer risk in non-smokers

Somatic DNA testing

• Analyzes DNA from cancer cells after diagnosis
• Helps guide treatment, such as targeted therapy or immunotherapy

Think of it this way:

• Germline = Prevention
• Somatic = Treatment

NGS Technology: Mapping your genes in high resolution

At the Bumrungrad Genomic Medicine Center, we use Next Generation Sequencing (NGS) to analyze hundreds of genes at once — through targeted multi-gene panels or deep whole-genome sequencing (WES, WGS).
Testing covers:

• Disease panels – for conditions that can be prevented or treated if detected early
• Wellness panels – for optimizing lifestyle choices based on your genetic profile

How can genetic testing help prevent lung cancer?

• Early awareness = timely action – enables tailored screening, such as low-dose CT scans at the right age
• More precise treatment – informs targeted drug use or immunotherapy
• Protecting your family – if an inherited mutation is found, relatives can be screened and monitored early

Who should consider genetic testing?

• Anyone who values proactive health planning and wants to understand their genetic risks

• People with a family history of cancer, especially:

  • Diagnoses at a young age (e.g., before 50)

  • Multiple types of cancer within the same family

• Individuals already diagnosed with cancer, where results can guide treatment choices

Note: Always seek genetic counseling before and after testing — from a Genetic Counselor or Clinical Geneticist — to ensure results are understood and applied correctly.
 

Are you ready… to understand your body at its deepest level?

Your genes cannot be changed. But what you choose to do today can shape your health tomorrow. Unlock the secrets in your DNA, and use that knowledge as a compass to make informed, life-changing decisions.
 
Let your genes tell the story of a future where you stay one step ahead of disease.
Book your appointment at the Bumrungrad Genomic Medicine Center, where our expert physicians and genetic specialists are ready to provide complete, personalized care.
 
 
Reviewed by Col.Asst.Prof.Dr. Kitti Buranawuti
Bumrungrad Genomic Medicine Center