Can your genes influence your risk of lung cancer? Understanding the role of genetic testing

Smoking remains the leading cause of lung cancer. But a growing number of people who have never smoked are now being diagnosed with the disease. In India, non-smokers account for an estimated 40 to 50% of all lung cancer cases, and some studies put the figure among Indian women as high as 83%. This has pushed doctors to look beyond the usual risk factors. Genetics is now part of that picture, helping explain why some people develop lung cancer despite no smoking history, and opening up options for earlier detection and more targeted drug treatment.

Can your genes increase disease risk?

Your genes carry the instructions that help cells grow, repair themselves, and function normally. Sometimes, variations or mutations in genes can disrupt their normal functions. This can involve partial or complete loss of gene function, or uncontrolled gain of gene function, such as extra copies or amplifications, which can be a primary cause of lung cancer.

In general, there are two types of genetic changes linked to cancer, namely inherited and acquired. The inherited (germline) mutations are transferred from parents to children through families. “Examples of a few hereditary cancers are breast, ovarian, colon, rectal, pancreatic and prostate”, Dr Prashanth Bagali, Head of Scientific Affairs – Oncology and Rare Diseases, MedGenome Labs Ltd., tells Health Shots. However, germline risk of lung cancer is uncommon but may increase a person’s susceptibility to certain cancers. The second, and far more common, are acquired (somatic) mutations.

These develop during a person’s lifetime due to factors such as tobacco smoking, secondhand smoke, air pollution from industrial toxic exhaust, environmental pollution from radioactive gases, workplace chemicals like asbestos, arsenic, nickel, chromium, diesel exhaust, organophosphorus insecticides, or simply ageing due to extended exposure and low immunity. These mutations occur only in the tumour and are not inherited or passed on to children.

Having a close family member with lung cancer may not directly increase your risk. However, shared lifestyle, breathing in smoke from other people’s cigarettes or beedi and environmental factors often contribute alongside genetic risk factors. Sometimes hereditary lung diseases, namely cystic fibrosis, familial pulmonary fibrosis or alpha-1 antitrypsin deficiency, exhibit symptoms like lung cancers. Therefore, it is critical to consult your doctors about specific genetic investigations and family counselling.

Why is genetic testing important?

Once lung cancer is diagnosed, many oncologists order genetic or genomic testing on the tissue biopsy removed from the lung tumour. This isn’t about inherited risk. It’s about analysing genetic driver mutations and hotspots in the lung tumour. To scan for key gene mutations, doctors are using advanced genetic testing, like next-generation sequencing (NGS). They are usually looking for changes in genes such as ALK, BRAF, EGFR, KRAS, and TP53, among others. The presence or absence of these molecular signatures determines prognosis, treatment guidance, drug selection and patient management.

Say a patient’s tumour turns out to have an EGFR mutation; doctors can prescribe drugs designed to target that specific mutation. If the tumour has an ALK rearrangement instead, a different set of targeted medicines may work better. Earlier standard chemotherapy drugs had significant deleterious side effects on healthy tissues.  However, targeted drugs and personalised treatments target the lung cancer-causing genes more effectively in patients who qualify.  Targeted drugs exhibit fewer side effects, since they go after cancer cells rather than healthy tissue.

Significance Beyond Treatment

Genetic testing also helps doctors gauge how aggressive a tumour is likely to be, how it might respond to the chosen treatment over time, and whether resistance is starting to build. Some of these changes can even be picked up through a blood test, a liquid biopsy, cutting down on the number of tissue samples required from a patient, making the process less invasive, and enabling doctors to manage the disease more precisely with timely insights. As access to genetic testing widens, more patients can be diagnosed earlier and receive treatments that are tailored to the specific genetic changes driving their cancer.