{Dr. Nilanju Sarmah, Head R&D and Academics, Metropolis Healthcare Limited}
Lung cancer is the leading cause of cancer-related deaths worldwide, more common in men and third in prevalence among women. It’s mainly classified into non-small cell lung cancer (NSCLC), which makes up 85% of cases, and small cell lung cancer (SCLC), a more aggressive form. Survival rates are low, with only 40% surviving one year after diagnosis, and just 10% after ten years. This poor prognosis is due to late-stage diagnosis, as early-stage lung cancer often has no symptoms or only mild, nonspecific ones. Genetic and familial factors also play a role in lung cancer risk.
A family history of lung cancer, especially in first-degree relatives, increases an individual's likelihood of developing the disease. This risk is even higher if multiple family members are affected or if the cancer appears at an early age in relatives. Although shared environmental and lifestyle factors within families contribute to this increased risk, recent research highlights a significant genetic component, particularly in cases of early-onset lung cancer or multiple primary lung cancers.
Despite extensive research into genetic predisposition, few specific gene variants have been conclusively linked to a high risk of lung cancer. One exception is Li-Fraumeni syndrome, a rare inherited condition caused by germline mutations in the TP53 gene, which is typically associated with sarcomas, breast cancer, brain tumours, leukaemia, and other cancers, but can also predispose individuals to lung cancer. Other rare genetic syndromes have been linked to increased lung cancer risk, including Neurofibromatosis type 1 (associated with mutations in the NF1 gene) and hereditary breast and ovarian cancer syndrome (caused by mutations in the BRCA1 and BRCA2 genes). Though these syndromes are more commonly associated with other cancers, individuals with these conditions may also face a heightened risk for lung cancer.
Another notable genetic factor is certain inherited mutations in the EGFR gene. Though rare, these mutations, such as the T790M variant, may increase the risk of lung cancer by promoting genetic instability, making cells more prone to mutations and tumorigenesis. However, the precise mechanisms by which these variants contribute to lung cancer risk remain unclear, and their rarity and low penetrance make both detection and management challenging.
Genetic testing has become an increasingly important tool in understanding the risk factors associated with lung cancer. While environmental factors, particularly smoking, are well-established contributors to the development of lung cancer, genetic predispositions are gaining attention for their role in both familial and sporadic cases of the disease. By identifying specific genetic mutations and hereditary syndromes, genetic testing can help assess an individual's risk for developing lung cancer, guide early detection efforts, and inform personalized treatment approaches. Individuals who develop lung cancer at an unusually young age, especially those with no significant history of smoking or other environmental exposures, may have an underlying genetic predisposition.
Additionally, some individuals may develop multiple primary lung cancers, which suggests a hereditary genetic factor. These cases often prompt further investigation through genetic testing to identify potential mutations that may increase cancer risk. Genetic testing plays a crucial role in identifying individuals at higher risk for lung cancer, particularly those with a family history of the disease or a history of early-onset cancer. Here are some key aspects of genetic testing in lung cancer. Genetic testing helps assess lung cancer risk and guide treatment decisions. For example, patients with EGFR mutations may benefit from targeted therapies like EGFR inhibitors (e.g., erlotinib, gefitinib), improving treatment outcomes. While valuable, genetic testing has limitations, as many mutations are rare and their role in disease development is unclear. Most lung cancers result from a complex mix of genetic and environmental factors.
Genetic testing is most useful for individuals with a strong family history or early-onset lung cancer. Genetic testing is increasingly important for both assessing risk and guiding treatment. It helps identify individuals at higher risk and enables targeted therapies, especially for mutations like EGFR. However, many lung cancers result from a mix of genetic and environmental factors, and the clinical significance of rare mutations is still being studied. Despite these challenges, genetic testing holds promise for early detection, personalized treatment, and improved outcomes.
