Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives
Why Is There An Increase In Lung Cancer Among Women Who Have Never Smoked?
Lung cancer cases are increasing in people who have never smoked, especially in women, a new study by the World Health Organization's cancer agency has found.
The findings, published in The Lancet Respiratory Medicine, reveal that lung adenocarcinoma, the most common type of lung cancer among non-smokers, accounts for nearly 60% of lung cancer cases in women compared to 45% in men.
About 2.5 million new lung cancer cases were diagnosed worldwide in 2022 – an increase of 300,000 since 2020. The study suggests that environmental factors, particularly air pollution, along with genetic predisposition and immune responses, may be driving this rise in non-smoking-related lung cancer.
One of the most significant risk factors for lung cancer in non-smokers is genetic mutations, especially mutations in the EGFR gene. This gene provides instructions for producing a protein on the surface of cells involved in growth and division.
Mutations in this gene drive uncontrolled cell division and tumour growth. They are found in 50% of lung adenocarcinomas in non-smoking Asian women and 19% in non-smoking western women – compared with 10–20% in non-smoking men.
Advances in genetic testing have made it easier to detect these mutations. However, rising exposure to air pollution, which is known to trigger EGFR mutations – may also be contributing to their increasing prevalence.
Other genetic changes that drive tumour growth include mutations in the genes ALK and ROS1, which are found in about 5% of lung cancer cases in non-smokers. These mutations are more often seen in younger non-smoking women, particularly in Asia. Thankfully, improved screening programmes, especially in east Asian countries, have helped detect these mutations more frequently.
Mutations in TP53, a crucial tumour-suppressing gene, also appear to be more commonly found in non-smoking women than in men. This gene prevents cells from becoming cancerous, and its mutation leads to out-of-control cell growth. The hormone oestrogen can interact with TP53 mutations, making lung cancer more likely to develop in women over time.
Another gene that is worth mentioning is KRAS. Mutations in this gene are usually associated with smoking-related lung cancer, however, they are increasingly being found in non-smokers – particularly women.
Recent studies suggest that exposure to tiny particles in the air, or PM2.5 (so-called because they are 2.5 micrometres or smaller) may be responsible for these mutations in non-smoker women.
Since PM2.5 levels continue to rise in many towns and cities, exposure to these particles could be another factor not only in lung cancer but also in other types of cancers in women.
In addition to genetic predisposition, hormone fluctuations may influence tumour growth in women. Oestrogen receptors are found in lung tissue, and experimental studies suggest that oestrogen promotes tumour growth. Studies have shown.) that women who receive hormone-replacement therapy (HRT), have a lower risk of lung cancer compared with women not on HRT, suggesting that natural oestrogen cycles may provide some level of protection.
Chronic inflammationBeyond genetics and hormones, chronic inflammation could also explain why lung cancer is rising among non-smoking women.
Women are more likely to develop autoimmune diseases than men, and problems with the immune system can play a role in cancer. Persistent inflammation can cause repeated damage to tissues, leading to changes in DNA and promote abnormal cell growth, all of which raise the risk of cancer.
Women with autoimmune diseases like rheumatoid arthritis and lupus have a higher chance of getting lung cancer, possibly because of long-lasting inflammation in the lungs. Inflammatory molecules – like interleukin-6 and tumour necrosis factor-alpha – can exacerbate the cancer by helping tumour cells survive and spread.
Autoimmune diseases have been increasing globally, probably because of environmental changes, changes in diet and shifts in gut microbiomes (the constellation of microorganisms that live in our guts and play an important role in our health). Because women are disproportionately affected by autoimmune conditions, they may be more vulnerable to chronic inflammation-driven cancer.
As life expectancy increases, more women are accumulating years of immune system activation, leading to a higher risk of developing inflammation-related lung cancer. In addition, things like pollution, household chemicals and work-related exposures can make immune system problems worse, increasing the risk of cancer even more.
Air pollution has long been recognised as a significant factor in lung cancer risk, but emerging evidence suggests that women may be particularly vulnerable. Studies show that women's lung anatomy and function make them more susceptible to the harmful effects of pollutants. Women's lungs are smaller than men's, with narrower airways, which might cause more fine particles, like PM2.5, to get trapped in their lungs.
Small airways may cause more fine particles to become trapped in women's lungs compared to men. Fabián Ponce / Alamy Stock PhotoAdditionally, oestrogen has been shown to amplify inflammatory responses when exposed to pollutants, potentially making lung tissue more prone to damage that can lead to lung cancer.
Women are more exposed to air pollution than men, but in a different way. While men often face pollution from factory work, women spend more time indoors where toxic fumes from cooking and heating are more common.
Air pollution in the home, especially from things like wood, coal and kerosene, can raise the risk of lung cancer. Women working in places such as textile factories, beauty salons and hospitals are also more exposed to harmful chemicals that can damage the lungs. In rapidly growing cities, women are often in areas with high traffic and factory pollution.
More significantWomen are biologically more likely than men to develop certain genetic mutations that increase the risk of lung cancer. However, factors like rising pollution, changes in hormone levels, immune system imbalances and longer life expectancy are making these risks even more significant.
Recent research suggests that HPV, a virus, may also contribute to lung cancer in women, underscoring the need for further study and preventative measures.
Understanding the roles of immune, hormonal, genetic and viral factors is key to spotting lung cancer early, creating more effective treatments and developing better ways to prevent it.
The Four Stages Of Chronic Obstructive Pulmonary Disease (COPD)
COPD is a progressive lung disease with mild symptoms in the early stages that gradually worsen. Early diagnosis and treatment can help preserve lung function.
People with COPD often have trouble breathing, a persistent cough, and shortness of breath. COPD can be subdivided into stages or grades, depending on how far it has progressed.
It is most common in smokers and people over the age of 40.
Keep reading to learn about the four stages of COPD. We'll discuss the symptoms you can expect at each stage and potential treatment options.
The GOLD system previously classified COPD from stages 1 to 4 solely based on your lung capacity measured by a spirometry test. But the newest GOLD guidelines combine your spirometry results with subjective measures of your symptom severity to determine your level of risk based on their ABCD rubric.
A spirometer test involves exhaling into a machine called a spirometer. The machine measures how hard and quickly you can exhale.
Your doctor examines two numbers in your results: your force vital capacity (FVC) and your force expiratory volume in one second (FEV1). Your FVC is the total amount of air you can breathe out and FEV1 is the amount you breathe out in one second. A ratio of your FEV1/FVC needs to be less than 0.7 for a diagnosis of COPD.
Doctors grade your spirometry results from grade 1 (least severe) to grade 4 (most severe). In the old system, these grades correlate with stage 1 to stage 4 COPD.
Doctors determine the severity of your symptoms using either the British Medical Research Council (mMRC) questionnaire or the COPD Assessment Test (CAT).
Stage 1 COPD is considered mild. At this stage, you may not be aware that you have anything wrong with your lung function. A doctor assigns you with grade 1 COPD if your FEV1 is between 80 and 100% of your predicted value.
Symptoms
If you score grade 1 on your spirometry test, you may not have any noticeable symptoms. If you do have symptoms, you may develop a cough and increased mucus production. You may mistake the early stages of COPD for the flu.
Treatment
Your doctor may also recommend getting flu, COVID-19, and pneumonia vaccines to prevent illnesses that may worsen your respiratory symptoms.
Changing lifestyle habits that led to the development of COPD can potentially help slow the progression of your COPD.
Most people with COPD have a history of smoking. Quitting smoking and avoiding secondhand smoke are two of the most important things you can do to improve your outlook with COPD.
Your COPD is considered to be stage 2 when your FEV1 drops to 50 to 79% of your predicted value.
Symptoms
During stage 2, your symptoms worsen from stage 1. Your coughing and mucus production may become more severe, and you may experience shortness of breath when walking or exercising. Typically, it's in this stage that people realize that something is wrong and seek medical attention from a doctor.
Treatment
You may be given bronchodilator medication to increase airflow to your lungs.
Your doctor may recommend pulmonary rehabilitation, a program designed to increase your awareness about your condition. It's usually offered as a group class where you learn how to manage your condition better.
If you have a flare-up of symptoms, you may need to take steroids or oxygen.
By the time you reach stage 3, COPD is considered severe, and your forced expiratory volume is between 30 to 50 percent of your predicted value. You may have trouble catching your breath doing household chores and may not be able to leave your house.
Symptoms
By stage 3, you may get more frequent flare-ups, and your shortness of breath and coughing typically get worse. You will likely find you get tired easier than before.
Other potential symptoms can include:
Treatment
The treatment options for stage 3 COPD are similar to stage 2. You're more likely to need oxygen therapy at this stage.
Stage 4 is considered very severe. Your forced expiratory volume is less than 30% of your normal value, and your blood oxygen levels are also low. You're at risk of developing COPD complications like heart or lung failure.
Symptoms
By stage 4, you'll likely have frequent flare-ups that can be potentially fatal. You may have trouble breathing even when you're resting.
Treatment
Treatment options during stage 4 are similar to the previous stages. Your doctor may also recommend lung surgery to improve breathing. Surgical options include:
A grade 4 score on your spirometry test is the highest grade you can receive. This category is also sometimes referred to as end stage COPD.
For many people at this stage, quality of life is usually fairly low, and symptom flare-ups can be fatal.
Having COPD lowers your life expectancy. However, the amount that it affects your life expectancy depends on many factors, such as how far your COPD has progressed and whether you quit smoking or change the other lifestyle habits that lead to COPD.
An older 2009 study found that COPD led to a small reduction in life span for people who have never smoked, but a larger life span decrease for people who currently smoke or smoked in the past.
According to the researchers, a 65-year-old man who smokes would lose 3.5 years from their life expectancy for smoking, plus the following values for having COPD:
For former smokers, the reductions are:
For somebody who never smoked, the reductions are:
In a 2017 study, researchers followed a group of long-term smokers with COPD for 5 years. They found that participants who had died before a 5-year follow-up had a longer average smoking time and a lower prevalence of quitting smoking. The researchers concluded that smoking time may be related to COPD mortality rate, and quitting smoking has the largest potential to influence COPD outlook.
A 2020 study of 532 people with COPD at a hospital in Taiwan suggests that loss of life years can vary based on a person's GOLD stage:
This study did not distinguish by smoking history.
No matter how far your COPD has progressed, it's important to change the lifestyle habits that caused your COPD in the first place. The most important thing you can do is quit smoking. If you don't quit, you'll continue to damage your lungs, and your COPD will progress quicker than it would otherwise.
Eating a nutrient-rich eating plan filled with plenty of vegetables, healthy fats, protein, and unprocessed foods may help you manage your symptoms and maintain a healthy weight. Eating foods that cause bloating, like apricots or peaches, may worsen breathing problems in some people.
Regular exercise may help decrease symptoms of COPD by strengthening your respiratory muscles and improving your cardiovascular health. Your doctor may be able to suggest exercise that is safe for you.
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