Genetic alterations in Lung Squamous Cell Cancer: Kinds, risk factors, and further details
Non-Small Cell Lung Cancer (NSCLC) is a common type of lung cancer, and like many cancers, its development can be linked to genetic mutations. These mutations can lead to issues within the cell, such as uncontrollable cell growth, turning off the cell's ability to die off or divide at the correct time, and turning on the cell's ability to divide, reproduce, or grow.
Genes provide the genetic makeup of cells and determine their functions, including when to reproduce and when to die off. Common genetic mutations associated with NSCLC include KRAS, EGFR, ALK rearrangements, TP53, STK11, KEAP1, and PIK3CA mutations.
The KRAS gene mutation, which mainly affects individuals who have smoked, accounts for about 20-30% of all NSCLC cases. EGFR mutations, found in approximately 10-20% of NSCLC patients worldwide, are notably higher in East Asian populations. ALK gene rearrangements, affecting about 5% of all individuals living with NSCLC, are more common among those who do not smoke and young people.
TP53 mutations, very common as co-occurring tumor suppressor gene alterations in NSCLC, are present in about 50% of cases. STK11 and KEAP1 mutations, also common co-mutations impacting prognosis and therapeutic resistance, are frequently observed in NSCLC tumors. PIK3CA mutations, though less common than KRAS or EGFR mutations, contribute to NSCLC pathogenesis and may co-occur with other mutations.
Of all people living with NSCLC, about 5% have a MET gene mutation, and this mutation is often more aggressive than NSCLC cases where the mutation is not present. The BRAF gene mutation, common in individuals who used to or currently smoke, affects about 10% of those with NSCLC. About 1% of individuals living with NSCLC have the ROS1 gene mutation, and it primarily affects young people who do not smoke.
Genetic or biomarker testing is recommended after a diagnosis of NSCLC to identify the responsible gene mutation for targeted treatment. Treatment for NSCLC can depend on which genes have mutated, and targeted therapies may be an option for those with genetic mutations. For example, EGFR and ALK mutations have approved targeted therapies with tyrosine kinase inhibitors (TKIs), while KRAS mutations, though prevalent, have historically been difficult to target.
Smoking is the most common risk factor for NSCLC, but other factors include radon, secondhand smoke, air pollution, asbestos, diesel exhaust, chemical exposure, and inherited or acquired gene mutations. People at risk of an inherited form of NSCLC should consult a doctor about screening frequency.
Clinical trials for NSCLC treatment have several stages, with the first involving the smallest number of participants and the third being closer to medication release for prescription use. Targeted drug therapy for NSCLC is undergoing clinical trials to determine its effectiveness and safety in the general population. Individuals may wish to discuss clinical trial options with their doctor.
A biomarker test involves a biopsy, which can be performed using a long needle, bronchoscope, or other tools. The time to receive test results can depend on sample size, laboratory, and office taking the sample.
Inheriting gene mutations from parents increases the risk of developing NSCLC. TP53 is a gene responsible for helping suppress damaged cells and preventing cancer. EGFR is a protein present on the outside of the cell that helps the cell divide and grow, and up to 23% of all NSCLC cases involve the EGFR gene mutation.
It is essential to note that while this article provides an overview of the common genetic mutations associated with NSCLC, the specific prevalence rates can vary by mutation and population. For accurate and personalised information, individuals are advised to consult their healthcare provider.
- A newly diagnosed Non-Small Cell Lung Cancer (NSCLC) patient may have genetic mutations such as KRAS, EGFR, ALK rearrangements, TP53, STK11, KEAP1, and PIK3CA, which can affect cell functions and lead to the disease.
- The KRAS gene mutation, common among smokers, accounts for about 20-30% of all NSCLC cases, while EGFR mutations, notably higher in East Asian populations, are found in approximately 10-20% of NSCLC patients worldwide.
- ALK gene rearrangements, affecting about 5% of all individuals living with NSCLC, are more common among non-smokers and young people.
- TP53 mutations, present in about 50% of NSCLC cases, are common co-occurring tumor suppressor gene alterations and are associated with a higher risk of the disease.
