Lung cancer has long been associated with older male smokers, but emerging data tells a more complex story. Younger women are being diagnosed with lung cancer at higher rates than men in certain age groups, such as ages 35 to 65, and non-smoking women face a higher relative risk than non-smoking men.
We spoke to two specialists, an oncologist and a thoracic surgeon, about what is driving this trend and why "never-smoker" should never be equated with "no risk."
What the data shows
"Globally, lung cancer in never-smokers accounts for a substantial proportion of cases, and women constitute a disproportionately large share of this group," says Dr. Sunny Jain, Clinical Director and Head, Medical Oncology, Marengo Asia Hospitals Faridabad. Indian studies, he says, have consistently shown that never-smoking patients with lung cancer are more likely to be women, younger, and diagnosed with adenocarcinoma.
The important message, Dr. Jain says, is that "absence of a smoking history should not lead to a low index of suspicion, particularly when a woman has persistent or unexplained respiratory symptoms."
Dr. Kamran Ali, Associate Director, Thoracic Surgery and Lung Transplant, Max Super Speciality Hospital, New Delhi, offers a nuanced take on whether this is a genuine rise or simply better detection. "Both are true, and it is worth saying so precisely rather than picking one side," he says.
"Global and Indian tumor registry data do show a real increase in lung cancer among never-smoking women and in younger age bands, not fully explained by smoking trends, which are falling in urban Indian women," Dr. Ali explains, adding that it is part signal, part better detection.
How this cancer looks different
In terms of histology, it is "predominantly adenocarcinoma," versus "squamous cell/small cell more common in smokers," Dr. Ali says. Presentation is "often asymptomatic, found incidentally on imaging done for something else, or vague symptoms (fatigue, mild cough, back pain from pleural involvement)," he explains.
He also points to a distinct mutation profile, with much higher EGFR mutation rate (especially in East/South Asian women), ALK rearrangements, which he describes as "actionable targets that change treatment entirely."
The role of EGFR mutations in treatment
"Never-smoking women with lung adenocarcinoma are enriched for actionable molecular alterations, particularly EGFR mutations," says Dr. Jain. "An Indian study of 907 patients with lung adenocarcinoma, published in PLOS ONE in 2013, reported EGFR mutations in 23% of patients overall, with a higher frequency among never-smokers than smokers-29.4% versus 15.3%," he says.
"If an activating EGFR mutation is identified, targeted therapy becomes the key treatment strategy rather than empiric immunotherapy," according to Dr. Jain.
Dr. Ali's data reinforces this picture. "East Asian and Indian never-smoking women show EGFR mutation rates of 40–60%+ vs. ~10-15% in Western smoker-associated cancers," he says, calling EGFR and genetic susceptibility "the best-supported biological factor" behind the trend.
Why treatment response differs
Smoking-related lung cancers generally accumulate a larger number of tobacco-associated genetic alterations and may therefore have a higher tumour mutational burden and greater potential immunogenicity. "A meta-analysis published in Frontiers in Immunology in 2021... found that the benefit from immune-checkpoint inhibitors was generally greater among smokers than never-smokers," Dr. Jain says.
This does not mean immunotherapy is ineffective in never-smokers, he clarifies. "Rather, it reinforces the principle that in a never-smoking woman with advanced adenocarcinoma, we should first establish whether there is a targetable driver mutation. If an actionable alteration such as EGFR or ALK is present, targeted therapy generally takes priority over an immunotherapy-first strategy," he explains.
Risk factors specific to Indian women
In Indian women, Dr. Jain says he particularly focuses on "biomass and solid-fuel exposure, household air pollution, secondhand tobacco smoke, outdoor air pollution, occupational/environmental exposures and family history."
His counselling message is that 'never-smoking' should not automatically be equated with 'no risk.' A patient's lifetime environmental exposure history is important.
Dr. Ali's findings align closely with this. "Indoor air pollution / cooking fumes" are backed by "solid epidemiological evidence, especially solid biomass fuel and high-heat oil frying (PAHs from mustard oil frying, especially in poorly ventilated kitchens)," he says.
Should non-smoking women be screened?
"At present, I would not recommend indiscriminate low-dose CT screening for every never-smoking woman, because there is not yet sufficient evidence that population-wide screening of this group provides more benefit than harm," Dr. Jain says.
"For India, I believe the immediate priority should be risk awareness and earlier clinical evaluation rather than blanket CT screening," he adds. A persistent cough, unexplained breathlessness, recurrent or non-resolving pneumonia, haemoptysis, unexplained chest pain or unexplained weight loss should not be dismissed simply because the patient has never smoked.
The larger message is that lung cancer is not synonymous with smoking. In India, particularly among younger women who have never smoked, we need to think beyond tobacco exposure, recognise environmental and genetic risk factors, investigate persistent symptoms earlier, and use molecular testing to ensure that patients receive the treatment their tumour biology demands.
