Abstract

While lung cancer is well established as being strongly associated with smoking, research explored in this paper demonstrates the fact that there are a variety of diverse factors that can contribute to lung cancer other than smoking. Recently, we have seen an increase in cases of lung cancer in women who do not smoke, specifically in East and South Asia, suggesting influences of both geographic and biological factors. The research illustrates that there are several contributors to lung cancer in non-smoking women. This research paper considers the evidence to explore the reasons why Asian women are developing lung cancer at increasing rates, despite smoking less than a hundred cigarettes in their lifetime (qualifying as “never-smokers”). This review paper explores environmental exposures such as cooking fumes, use of biomass fuels and radon gas. The interaction of these environmental factors with genetic susceptibility, including higher rates of EGFR mutations in Asian populations, combined with biological factors such as hormonal influence, including oestrogen receptor signalling that may cause and promote tumour growth, are also examined.  Evidence from research suggests that these interactions could be a possible explanation for the disproportionately high number of lung cancer cases in non-smoker Asian women. Better understanding of different risk factors and their interactions will enable the development of more effective prevention and treatment strategies for non-smoker Asian women. 

Introduction

Lung cancer is a disease commonly recognised as being associated with cigarette smoking as past records show 80-90% of lung cancer cases were caused by cigarette smoking (Warren & Michael, 2013). While a decrease in smoking rates has reduced the number of cases of lung cancer, the number of cases in non-smoker patients has risen dramatically, with an estimated 10-25% of lung cancers worldwide now occurring in people who have never smoked (Couraud et al., 2012). Emerging evidence suggests that these cases of lung cancer in non-smoking patients can be viewed as a distinct clinical and molecular entity, indicating the different epidemiology of cancer which is not initiated by tobacco exposure. In recent decades, a distinct pattern has emerged showing significant gender and geographic differences for lung cancer in non-smokers: lung cancer in non-smoking women in Asia comprises approximately 60-80% of the cases of lung cancer (Dubin & Griffin, 2020). Smoking prevalence amongst women in this region has historically been low, with fewer than 5% reporting current tobacco use, and exposure to second-hand smoke in the home has also remained relatively uncommon (Yang et al., 2022). Therefore, researchers have begun to investigate other environmental and biological causes which could be associated with this rise. These factors include environmental differences, such as higher exposure of Asian women to cooking oil/fumes, radon gas and air pollution, coupled with hormonal factors and genetic susceptibility, vividly highlighting the multifactorial nature of this disease. For these reasons, this paper argues that the disproportionately high rates of lung cancer in non-smoking Asian women is likely caused by chronic environmental exposures (like cooking fumes, biomass fuels and radon exposure) initiating genetic and cellular mutation, combined with biological susceptibility (more prevalent in Asian population) such as hormonal influence and pre-existing genetic mutations such as EGFR. Understanding the interlink between different risk factors is crucial because diseases such as lung cancer are not just caused by any one factor. The interaction between multiple environmental and biological factors can increase risk, making certain groups more vulnerable to lung cancer. Therefore, recognising connections between several factors allows healthcare professionals to take more efficient preventative measures, accelerate detection in individuals who may seem at low risk and design better treatments that target both environmental damage and biological factors, ultimately improving outcomes. 

Several environmental factors increase the risk of lung cancer development; however, cooking fumes and radon gas are proposed as major contributors to disproportional rates of lung cancer in non-smoker Asian women (Xue et al., 2016; Urrutia-Pereira et al., 2023). Indoor cooking oil fumes and use of biomass fuels release carcinogens, like particulates and aldehydes, deep into lungs where they cause DNA damage, oxidative stress and chronic inflammation (Xue et al., 2016). Radon gas exposure, especially in indoor settings, exposes individuals to ionising alpha radiation that causes DNA double strand breaks. Both of these environmental factors increase the chances of mutations in individuals, thereby acting as a risk factor for lung cancer. However, environmental factors alone may not be the cause of high rates as, regardless of geographical locations, non-smoking women experience higher rates of lung cancer than men, suggesting sex-specific vulnerability that may be amplified in Asian populations (Dubin & Griffin, 2020). Therefore, it can be argued that biological factors which can influence the likelihood of cancer development must also be considered in parallel to environmental contributors. Hormonal factors, particularly oestrogen and its receptors, may make non-smoking women biologically more susceptible to lung cancer by both increasing the chance that mutations arise and amplifying the growth of tumours that already carry oncogenic mutations (Siegfried et al., 2010). This paper will explore how environmental exposures, such as cooking fumes and radon gas, interact with biological factors, including hormonal influences and genetic susceptibility, to contribute to the disproportionately high rates of lung cancer in non-smoking Asian women.

Cooking Practices as a Risk Factor

A factor that may be considered as having contributed to this increase is air pollution from cooking practices in Asian cultures (WHO, 2009). While cigarette smoking remains the dominant global risk factor for lung cancer (responsible for around 60% DALYs globally), indoor air pollution from cooking practices also represent a major but often under-recognised environmental risk, particularly among non-smoking women in East and South Asia as it contributes to approximately 15% of DALYs in high-exposure regions (Xue et al., 2016). In many Asian households, women traditionally spend more time engaged in cooking activities, leading to prolonged and repeated exposure to cooking fumes (Xue et al., 2016). This exposure becomes especially significant in poorly ventilated kitchens and densely populated urban housing, where airborne pollutants accumulate over time (IARC, 2010).

CARCINOGENS FROM BIOMASS FUELS

In rural and lower-income regions, biomass fuels such as wood, coal, charcoal, crop residues and animal dung are commonly used for cooking and heating. The incomplete combustion of these fuels generates a complex mixture of harmful pollutants, including particulate matter (PM2.5), carbon monoxide, benzene, formaldehyde and polycyclic aromatic hydrocarbons (PAHs) (WHO, 2014). Many of these substances are established carcinogens. The International Agency for Research on Cancer has classified indoor emissions from household coal combustion as carcinogenic to humans (Group 1), based on strong epidemiological evidence linking exposure to lung cancer (IARC, 2010).

The biological mechanism underlying this association is well established. Fine particulate matter (PM2.5) is sufficiently small to penetrate deep into the alveoli of the lungs. Once deposited, these particles induce chronic inflammation and oxidative stress. PAHs present in biomass smoke are metabolically activated in lung cells into reactive intermediates that bind directly to DNA, forming DNA adducts. DNA adduct formation interferes with normal DNA replication and repair processes. If unrepaired or misrepaired, these alterations can result in permanent mutations in key regulatory genes, including proto-oncogenes and tumour suppressor genes (WHO, 2014). Over time, cumulative genetic damage may initiate carcinogenesis.

Chronic inflammation further contributes to tumour development. Persistent inflammatory responses lead to the release of cytokines and reactive oxygen species (ROS), which can promote additional DNA damage and stimulate cell proliferation (Multhoff et al., 2012). Increased cell turnover elevates the probability of replication errors, compounding mutation burden. Thus, biomass smoke acts both as a direct mutagen and as a tumour promoter through inflammatory pathways.

CARCINOGENIC EFFECTS OF INDOOR COOKING OIL FUMES

Even in urbanised and economically developed regions where biomass use has declined, another important exposure persists: cooking oil fumes. High-temperature cooking methods commonly used in East Asian cuisine, such as stir-frying and deep-frying, generate significant quantities of ultrafine particles and volatile organic compounds (Ko et al., 2000). When oils are heated to high temperatures, thermal degradation produces aldehydes (such as acrolein and formaldehyde), heterocyclic amines and PAHs (Chen et al., 2018). While all oils produce aldehydes when heated to high temperatures, the quantification of degradation product depends on the fatty acid composition and smoke point of the oil. Commonly used oils in Asian households are soybean and sunflower oil, both of which are high emitters of aldehydes during deep frying and stir-frying (Peng et al., 2017).  

These fumes are particularly concentrated in enclosed kitchens without effective ventilation systems. Epidemiological studies conducted in Taiwan, mainland China and Singapore have shown that non-smoking women exposed to frequent wok cooking fumes exhibit a significantly increased risk of lung adenocarcinoma (Ko et al., 2000). The risk is further amplified when mechanical ventilation, such as range hoods, is absent or rarely used (Xue et al., 2016).

INTERACTION OF COOKING PRACTICES WITH BIOLOGICAL SUSCEPTIBILITY

At a cellular level, aldehydes produced from overheated oils are highly reactive molecules that can directly damage DNA and proteins (Young et al., 2010). Acrolein, for example, forms DNA adducts and inhibits DNA repair enzymes, increasing genomic instability. In addition, ultrafine particles from cooking fumes can penetrate deeply into lung tissue, triggering oxidative stress and inflammatory signalling pathways similar to those observed in air pollution exposure.

An important feature of lung cancer in East Asian non-smoking women is the high prevalence of EGFR mutations (present in approximately 40-60% of Asian non-smoking women), particularly in adenocarcinoma cases (Shigematsu et al., 2005). Although cooking fumes do not selectively target the EGFR gene, chronic exposure increases overall mutation frequency within lung epithelial cells. A higher baseline mutation rate increases the statistical likelihood that activating mutations in EGFR may arise. Once such mutations occur, they can drive uncontrolled cell proliferation.

Furthermore, emerging evidence suggests that PM2.5 may function not only as a mutagen but also as a tumour promoter. Inhaled particulates can stimulate inflammatory mediators such as interleukin-1β, which may promote the expansion of pre-existing mutant cell clones. This implies that cooking-related pollutants may both initiate DNA damage and accelerate the growth of previously mutated cells, thereby contributing to cancer progression, especially in Asian women who experience higher exposure to these particulates from combustion fumes while cooking (Xue el al., 2016).

The disproportionate burden of lung cancer among non-smoking Asian women may partly reflect social and behavioural factors. In many households across China, Korea, Japan, India and Southeast Asia, women traditionally assume primary responsibility for food preparation. Consequently, lifetime cumulative exposure to indoor cooking emissions may be substantially higher in women compared to men. This is a major concern because even though very few women in the area smoke (only about 3-4%), their risk of lung cancer remains high (Sung et al., 2021).

URBANISATION AND INDOOR EXPOSURE RISK

Although biomass use may decline with economic development, as households transition away from traditional biomass fuels, many families move into high-rise apartments with limited natural ventilation and the absence of an effective kitchen exhaust system, allowing cooking-related pollutants to accumulate indoors. Without adequate airflow or modern exhaust systems, ultrafine particles accumulate and prolong exposure duration (Xue et al., 2016). Epidemiological studies in Chinese non-smoking women show that indoor air pollution from frequent cooking, solid fuel use and poorly ventilated housing is strongly associated with lung cancer risk (Mu et al., 2014). 

Indoor cooking exposure represents a biologically plausible and epidemiologically supported contributor to lung cancer among non-smoking Asian women. Biomass smoke introduces established carcinogens (PM2.5, carbon monoxide, benzene, formaldehyde and PAHs) capable of causing direct DNA damage, while cooking oil fumes generate reactive aldehydes and ultrafine particulates that induce oxidative stress and chronic inflammation (Lai et al., 2014). These processes increase mutation rates and may interact with genetically susceptible pathways such as EGFR-driven tumour growth (Lai et al., 2014).

However, similar to all other risk factors, cooking exposure alone does not fully account for regional patterns of disease. Lung cancer in non-smoking Asian women is best understood as a multifactorial condition arising from the cumulative impact of multiple indoor environmental carcinogens interacting with biological susceptibility and socio-cultural exposure patterns. In addition to cooking-related pollutants, other less visible but significant household environmental exposures may further elevate risks.

Radon Gas as a Risk Factor

Another environmental factor that elevates the risk of lung cancer for the female Asian population is exposure to radon gas. Radon gas is a radioactive noble gas which forms naturally from the decay of uranium (which is a metal typically present in rocks and soil in the Earth’s crust). During uranium’s radioactive decay, radium-226 is produced and further decay results in radon gas being released (WHO, 2009). Due to its odourless, colourless and tasteless characteristics, it necessitates detection by specialised equipment only. This process is unpreventable and continuous; therefore, radon is always present in the environment to some degree (Darby et al., 2005). Although radon exposure itself is not biologically gender or geography specific, cultural patterns in Asia populations may provide an explanation for higher radon exposure to women. Culturally, in Asia, women spend prolonged time in poorly ventilated domestic environments compared to men, leading to greater cumulative exposure.

ISOTOPES OF RADON

There are three main isotopes of radon: radon-219, radon-220 and radon-222. Of these, radon-222 is the most significant for human health due to its relatively short half-life of just 3.8 days which makes it unstable but sufficiently long enough for it to migrate through the soil and enter buildings before it decays (ICRP, 2010). 

RADON PATHWAY

Radon gas moves through small cracks and pores in rocks and soil. It then enters buildings through gaps in service pipes, cracks in building foundations, construction joints, drains and insulation cavities inside walls. It may dissolve in groundwater and contaminate isolated water sources, such as private wells, and gain access to people’s residences (WHO, 2009). 

The presence of radon becomes problematic when it accumulates in homes at ground level or in the basement, where there is a lack of cross ventilation. In colder countries such as Denmark, Sweden and Norway, modern urban building best practice encourages energy conservation but limits the exchange of air to conserve heat. This has the unintended effect of radon accretion by trapping it indoors (Darby et al., 2005).

RADIOACTIVE INSTABILITY AND ALPHA PARTICLE EMISSION

Radon-222 decays into a series of radioactive particles known as radon “progeny” or “daughter”. Herein lies the biological danger of its radioactive instability. Alpha particles are emitted during this decay. Alpha radiation is characterised by low penetration and cannot travel deep inside tissue. However, its ionising power is high. Upon inhalation, radon progeny attaches itself onto the bronchial epithelium of the lungs. As the particles continue to decay, alpha radiation is released in-situ (in the bronchial epithelial cells) onto neighbouring lung cells (ICRP, 2010).

MOLECULAR MECHANISMS OF DNA DAMAGE AND CARCINOGENESIS

Alpha particles cause significant DNA damage at the molecular level. They do this due to their high ionisation density, emitting a high number of particles over a small, localised area. The alpha particles act on chemical bonds of DNA and cause double-strand DNA breaks, considered the most serious type of DNA damage (Little, 2000). 

Although cells are equipped with DNA repair capability, the repair work is not always exactly correct due to an inaccurate template or the cell’s high-volume workload, which could mean some mistakes slip through. This incorrect repair may result in permanent mutation. If this mutation occurs in proto-oncogenes or tumour suppressor genes, normal cell renewal cycles are disrupted leading to tumour formation. If lung cells amass sufficient genetic mutation, they become cancerous. In this way, radon exposure provides a clear mechanism which links environmental radiation to lung cancer (UNSCEAR, 2006).

EPIDEMIOLOGICAL EVIDENCE LINKING RADON TO LUNG CANCER

Epidemiological evidence strongly suggests that radon is carcinogenic. Historic research regarding underground miners exposed to concentrated amounts of radon demonstrated a clear correlation between the amount of exposure and magnitude of effect, often called the dose-response effect, in these individuals (Lubin et al., 1995). 

More recently, studies have demonstrated that even lower levels of residential exposure are associated with increased risk of lung cancer, making it not only an occupation but also a domestic hazard (Darby et al., 2005). In fact, for every 100Bq/m³ increase in radon concentration found in residences, lung cancer risk increases by 7%, giving further weight to the notion that radon gas exposure even at very low levels is directly proportional to lung cancer risk (Zhang et al., 2012). 83% of Southern Asian women have never smoked, compared to only 15% in the United States, but they make up 53% of women with lung cancer globally (Couraud et al., 2012; Thun et al., 2008). This statistic suggests a much stronger environmental role. 

In China, about 20% of lung cancer mortality is amongst non-smokers (Chen et al., 2015), and though radon gas has not been isolated in these studies as the main cause of these deaths, there is growing speculation as domestic radon gas surveys accumulate compelling data that suggests radon may be a more significant player than previously surmised (WHO, 2009). According to the World Health Organisation, radon exposure is responsible for between 3-14% of all lung cancers globally in non-smokers (WHO, 2009).

GEOLOGICAL AND ARCHITECTURAL DETERMINANTS OF RADON EXPOSURE IN EAST ASIA

Several factors, for instance modern architecture and underground water reserves, can help explain why Radon exposure is significant in parts of Asia. Certain regions in Asia have a high concentration of igneous rock and granite rock in uranium. Naturally, higher uranium concentrations result in high Radon gas production. In China, for example, some studies have evaluated indoor Radon exposure and revealed elevated levels compared to the global average (Zhang et al., 2012). 

Additionally, modern architectural preferences coupled with a rapid increase in urbanisation contribute to higher radon exposure. Affordable residential high rise buildings in ever expanding cities often boast underground parking facilities and filtration systems which prioritise conservation of heat rather than cross ventilation. This inadvertently increases risk of radon exposure by trapping radon gas indoors (Darby et al., 2005). 

Traditionally, in some regions, women make up a higher percentage of homemakers, and therefore, it is not inconceivable that they may be in receipt of a steadier exposure of domestically trapped radon gas. Though modern times have seen an increase in the size of the female workforce, cultural and generational patterns result in a higher cumulative exposure to radon gas compared to men. This is particularly true for older women but also for many from the younger generation as the bulk of domestic labour and child care responsibilities fall to women (International Labour Organisation, 2018; United Nations ESCAP, 2019).

Without regulation and public health policies designed to mitigate the harmful effects of radon gas, such as periodic radon testing, exposure to radon gas is likely to persist undetected (WHO, 2009). Therefore, socio-cultural norms in concert with rapid urbanisation and thermally efficient architecture may help to shed light on why radon gas is a particularly crucial factor in lung cancer in non-smoking Asian women.

GENETIC SUSCEPTIBILITY

An important aspect of lung cancer in Asian non-smoking women is its genetic profile. The mutation in the tumours of many such women are in the epidermal growth factor receptors (EGFR). These mutations appear to be more common in Asian than in Western populations (Shigematsu et al., 2005). Although radon does not specifically target EGFR genes, radiation increases mutation rates within the cells that have been exposed. Increased mutations mean that EGFR mutation may occur, driving tumour growth. Therefore, underlying genetic susceptibility interacts with radon exposure to propel cancer development (UNSCEAR, 2006).

INTERACTION WITH AIR POLLUTION

Crucially, radon does not act in an isolated fashion. Outdoor pollution in some Asian megacities is very high. Annually, megacities such as Beijing and Shanghai are obnubilated by an average of up to 100 µg/m³ of fine particle matter, with peak levels exceeding 300 µg/m³. These are alarming levels compared to WHO annual guidelines of just 5µg/m³ (WHO, 2021). Sustained inhalation of air with high fine particulate matter causes inflammation in lung tissue. Coupled with DNA damage caused by radon exposure, exposure to environmental outdoor air pollution may increase the risk of lung cancer (IARC, 2013). 

The evidence for the causal relationship of radon exposure to lung cancer is strong (WHO, 2009; Darby et al., 2005). It is important, however, to treat lung cancer incidence in East Asian women in particular as a multifaceted threat. Like cooking practices, radon exposure alone does not explain the high incidence of lung cancer as some areas are known to have low concentrations within these high-density radon regions, but the incidence of lung cancer is largely uniform and appears unperturbed by this absence (Sung et al., 2021).

Hormonal Influence as a Risk Factor

While environmental carcinogens such as cooking fumes and radon gas are major contributors to high incidence of lung cancer in Asians, they alone do not explain the disproportionate burden among women. Therefore, we should consider biological factors that may influence how the environmental damage is translated into cancer development. Hormonal factors present a biologically plausible contributor to lung cancer in non-smoker Asian women, particularly the impact of oestrogen and its intracellular oestrogen receptors (ERs) on cell division and interaction with proto-oncogenes and signalling pathways. Oestrogen receptors (ER alpha and beta) are expressed in both normal lung tissue and lung tumours, making hormonal influence a possible cause or contributor (Pallis & Syrigos, 2013). ERs may increase the chances of genetic mutation, making them initiators for lung cancer but also their crosstalk with mutated oncogenes like EGFR can cause tumours to expand quickly, making existing lung cancer progress as well. This highlights the need to consider hormonal signalling as an intrinsic factor that may be responsible for both the cause and progression of a tumour.  

OESTROGEN RECEPTORS AS TUMOUR INITIATORS

ERs may increase the chance of mutation in genes, including proto-oncogenes like EGFR, increasing the chances of developing a tumour. Oestrogen binds to ERs and their complex acts as a transcription factor, increasing expression of certain genes leading to higher rates of cell proliferation. From a carcinogenesis perspective, this increase in rate of cell division means more DNA replication, which directly increases the probability of mutations. If these mutations occur in proto-oncogenes, tumour suppressor genes or DNA repair genes (such as TP53, RB1, STK11 and ATM), they can be a direct cause of the development of a cancer (Cohen, 2024). This mechanism may be particularly relevant in non-smoking women in South Asia who are not exposed to tobacco carcinogens but can accumulate mutations from internal processes (e.g., normal replication errors, reactive oxygen species and endogenous hormones) over many years of cell division (Cohen, 2024). This biological susceptibility of oestrogen-driven proliferation in women coupled with environmental factors may be the cause of the relatively high cases of lung cancer among South Asian women (Lam, 2005).

OESTROGEN RECEPTORS AS TUMOUR AMPLIFIERS

Oestrogen signalling not only contributes to rapid tumour growth, but research also suggests that its interaction with EGFR pathways (crosstalk) appears to cause cancer to grow at a faster rate (Ribeiro & Freiman, 2015). Crosstalk is when two signalling pathways influence each other instead of acting independently. Similar to breast cancer development, estradiol binds to beta ER; it activates intracellular kinases (enzymes that phosphorylate proteins). The kinases phosphorylate EGFR, resulting in the activation of pathways like MAPK and PI3K/Akt which are directly responsible for cell division and proliferation (Clusan et al., 2023). These interactions directly result in amplified proliferation signalling, leading to enhanced growth, survival and resistance to apoptosis of the tumour. Furthermore, research by Marquez-Garban et al. (2019) has confirmed that silencing ER alpha or ER beta in NSCLC cells sharply reduced tumour cell proliferation, indicating ERs enhance growth of tumours. These mechanisms are especially significant in women who have a higher concentration of circulating estradiol (a form of hormone oestrogen) and higher beta ER expression in lung tissue. Therefore, oestrogen can promote tumour progression and might even contribute to resistance to treatments (Chakraborty et al., 2011). This is particularly relevant to South Asian non-smoker women who have higher rates of EGFR-mutated lung cancer. A report on the mutational landscape in non-small cell lung cancer of South Asian patients confirmed that South Asian non-small cell lung cancer (NSCLC) patients showed a significantly high burden of activating EGFR mutations – 33% in a South Asian cohort in the U.S. and a 22.5% in an Indian cohort (Roy et al., 2022). These values show a relatively high prevalence of EGFR mutations compared to typical Caucasian (European/Western ancestry) rates which are around 10-15%. While the scientific reason for higher rates of EGFR mutated cancers in Asian women remains unclear in research, epidemiological studies show that these mutations occur more frequently in women and in Asian populations than in other groups (Bell et al., 2008). The ability of ER signalling to enhance EGFR-driven proliferative and survival pathways strongly suggests that hormonal interaction may play a contributory role in tumour progression (Stabile & Siegfried, 2008).

Discussion

The combination of all factors discussed in this paper provides a better count for observed epidemiological patterns suggesting the higher rates of lung cancer in non-smoking Asian women. While exploration of hormonal influence provides an explanation for higher rates of lung cancer in non-smoking women in general, exploring how this biological susceptibility interacts with geographical environmental factors, such as cooking fumes and radon gas, may provide a clearer explanation for higher rates of lung cancer in Asian women. In biological susceptible tissue (due to oestrogen receptor signalling), exposure to environmental carcinogens (more prevalent in Asian households) may lead to a greater mutagenic impact to Asian women. This reinforces the idea that the combination of intrinsic hormonal susceptibility and environmental exposure contributes to the disproportionally high lung cancer rates in Asian non-smoker women. The environmental carcinogens explained may be a possible explanation for higher rates of EGFR mutations in female Asian lung cancer patients as they can exacerbate existing susceptibilities in women due to hormonal influence.  

However, as previously discussed, the underlying biological mechanisms for higher rates of EGFR mutated lung cancers in non-smoking South Asian women remain unclear in research (Roy et al., 2022). Further research must focus on molecular interactions between hormone signalling pathways and EGFR mutation frequency, particularly in the context of environmental carcinogens, such as cooking fumes and radon gas, which Asian women are more exposed to. Hormone driven increases in cellular division may enhance susceptibility to DNA damage, increasing replication errors (Chakraborty et al., 2011). Given the capacity of damage of these environmental exposures to induce genetic mutation, their interactions with intrinsic biological mechanisms present a plausible explanation for disproportionally high rates of lung cancer in non-smoking Asian women. Clarifying links between different environmental and biological factors will improve both biological and epidemiological understanding of risk factors leading to higher cases of lung cancer in non-smoking Asian women. Bridging this knowledge gap will also allow epidemiologists to develop more specific and targeted screening programmes for most of the vulnerable populations, ultimately improving early detection and patient outcomes.

Conclusion

In conclusion, lung cancer is not a disease caused by a single factor but a multifunctional disease arising from the interaction of multiple factors. The disproportionally high rates of lung cancer in Asian non-smoker women highlight the interaction between chronic environmental exposures, such as cooking fumes and radon gas, interacting with biological susceptibility, including hormonal influences, genetic mutations and crosstalk between oestrogen receptors and oncogenes like EGFR. Neither factors can be held responsible individually; instead it is their interactions that appear to define higher risks in this population. 

Understanding these intricate connections has real clinical implications. By recognising the interlink between these different factors, we increase our understanding of risks of lung cancer in women in different geographical locations. Knowledge of interactions between different risk factors is crucial for developing targeted prevention strategies, improving early detection and improving treatment approaches. Future research should continue to investigate the molecular and environmental mechanisms underpinning trends in spread of lung cancer around the world. Not only will this refine our biological understanding, but it will also translate into impactful reductions in lung cancer cases all around the globe. This knowledge can also help doctors and the healthcare system raise public awareness and screening levels, allowing lung cancer to be detected earlier, ultimately improving treatment outcomes and increasing survival rates.

Bell, D.W., Brannigan, B.W., Matsuo, K., Finkelstein, D.M., Sordella, R., Settleman, J., Mitsudomi, T. & Haber, D.A. (2008) ‘Increased prevalence of EGFR-mutant lung cancer in women and in East Asian populations: analysis of estrogen-related polymorphisms’, Clinical Cancer Research, 14(13), pp. 4079–4084.

Chakraborty, S., Ganti, A.K., Marr, A. & Batra, S.K. (2010) ‘Lung cancer in women: role of estrogens’, Expert Review of Respiratory Medicine, 4(4), pp. 509–518.

Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., Jemal, A. & He, J. (2015) ‘Cancer statistics in China, 2015’, CA: A Cancer Journal for Clinicians, 66(2), pp. 115–132. 

Chen, Y. C., et al. (2018) ‘Exposure to Cooking Oil Fumes and Lung Cancer in Nonsmoking Women’, Cancer Causes & Control, 29( 6), pp. 605–613.

Clusan, L., Ferriere, F., Flouriot, G. & Pakdel, F. (2023) ‘A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer’, International Journal of Molecular Sciences, 24(7), p. 6834.

Cohen, S.M. (2024) ‘Cell proliferation and carcinogenesis: an approach to screening for potential human carcinogens’, Front Oncol. (14)1394584.

Couraud, S., Zalcman, G., Milleron, B., Morin, F. & Souquet, P.J. (2012) ‘Lung cancer in never smokers – A review’, European Journal of Cancer, 48(9), pp. 1299–1311.

Darby, S., Hill, D., Auvinen, A., et al. (2005) ‘Radon in Homes and Risk of Lung Cancer: Collaborative Analysis of Individual Data from 13 European Case-Control Studies’, BMJ, 330(7485), pp. 223–227.

Dubin, S. & Griffin, D. (2020) ‘Lung cancer in non-smokers’, Missouri Medicine, 117(4), pp. 375–378.

IARC (2010) ‘Household Use of Solid Fuels and High-Temperature Frying’ in IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 100B, International Agency for Research on Cancer.

IARC (2013) ‘Outdoor air pollution: a leading environmental cause of cancer deaths’, International Agency for Research on Cancer [pdf]. <https://www.iarc.who.int/wp-content/uploads/2018/07/pr221_E.pdf>

ICRP (2010) ‘Lung Cancer Risk from Radon and Progeny and Statement on Radon’, International Commission on Radiological Protection Publication 115 [pdf]. <https://journals.sagepub.com/doi/pdf/10.1177/ANIB_40_1>

ILO (2018) ‘Care Work and Care Jobs for the Future of Decent Work’, International Labour Organization [pdf]. <https://www.ilo.org/sites/default/files/wcmsp5/groups/public/@dgreports/@dcomm/@publ/documents/publication/wcms_633135.pdf>

Ko, Y.-C., et al. (2000) ‘Lung Cancer among Nonsmoking Women in Taiwan: An Epidemiologic Study of Cooking Fumes’, Journal of the National Cancer Institute, 92(2), pp. 156–160.

Ko, Y. C., Cheng, L. S., Lee, C. H., Huang, J. J., Huang, M. S., Kao, E. L., Wang, H. Z. & Lin, H. J. (2000). ‘Chinese Food Cooking and Lung Cancer in Women Nonsmokers’, American Journal of Epidemiology, 151(2), pp. 140–147. 

Lai, C. H., Jaakkola, J. J., Chuang, C. Y., Liou, S. H., Lung, S. C., Loh, C. H., Yu, D. S. & Strickland, P. T. (2013) ‘Exposure to cooking oil fumes and oxidative damages: a longitudinal study in Chinese military cooks’, Journal of Exposure Science & Environmental Epidemiology, 23(1), pp. 94–100

Lam, W.K. (2005) ‘Lung cancer in Asian women—the environment and genes’, Respirology, 10(4), pp. 408–417.

Little, J.B. (2000) ‘Radiation carcinogenesis’, Carcinogenesis, 21(3), pp. 397–404.

Lubin, J.H., Boice Jr, J.D., Edling, C., Hornung, R.W., Howe, G.R., Kunz, E., Kusiak, R.A., Morrison, H.I., Radford, E.P., Samet, J.M., et al. (1995) ‘Lung cancer in Radon-exposed miners and estimation of risk from indoor exposure’, Journal of the National Cancer Institute, 87(11), pp. 817–827.

Márquez-Garbán, D.C., Chen, H.W., Fishbein, M.C., Goodglick, L. & Pietras, R.J. (2007) ‘Estrogen receptor signaling pathways in human non-small cell lung cancer’, Steroids, 72(2), pp. 135–143.

Milner, J., Shrubsole, C., Das, P., Jones, B. & Hamilton, I. (2014) ‘Home energy efficiency and radon related risk of lung cancer: modelling study’, BMJ, 348(7493).

Mu, L., Liu, L., Niu, R., Zhao, B., Shi, J., Li, Y., Scheider, W., Su, J., Chang, S.-C., Yu, S. & Zhang, Z.-F. (2013) ‘Indoor air pollution and risk of lung cancer among Chinese female non-smokers’, Cancer Causes Control, 24(3), pp. 439–450.

Multhoff, G., Molls, M. & Radons, J. (2012) ‘Chronic inflammation in cancer development’, Frontiers in immunology, 2(98).

Peng, C. Y., Lan, C. H., Lin, P. C. & Kuo, Y. C. (2017). ‘Effects of cooking method, cooking oil, and food type on aldehyde emissions in cooking oil fumes’, Journal of Hazardous Materials, 324(B), pp. 160–167. 

Ribeiro, J.R. & Freiman, R.N. (2014) ‘Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer’, J Steroid Biochem Mol Biol, 143, pp. 160–173.

Rodriguez-Lara, V., Hernandez-Martinez, J.M. & Arrieta, O. (2018) ‘Influence of estrogen in non-small cell lung cancer and its clinical implications’, Journal of Thoracic Disease (JTD), 10(1), pp. 482–497.

Roy, M., Bal, A., Gupta, N., Prasad, K.T., Wakelee, H.A. & Singh, N. (2022) ‘A brief report on the mutational landscape in non-small cell lung cancer of South Asian patients: Comparison at a US and an Indian Institution’, Lung India, 39(4), pp. 315–318.

Shigematsu, H., Lin, L., Takahashi, T., et al. (2005) ‘Clinical and Biological Features Associated with Epidal Growth Factor Receptor Gene Mutations in Lung Cancers’, Journal of the National Cancer Institute, 97(5), pp. 339–346.

Siegfried, J.M., Hershberger, P.A. & Stabile, L.P. (2009) ‘Estrogen Receptor Signaling in Lung Cancer’, Semin Oncol, 36(6), p. 524. 

Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. & Bray, F. (2021) ‘Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries’, CA: A Cancer Journal for Clinicians, 71(3), pp. 209–249.

Thun, M.J., Hannan, L.M., Adams-Campbell, L.L., Boffetta, P., Buring, J.E., Feskanich, D., Flanders, W.D., Jee, S.H., Katanoda, K., Kolonel, L.N. & Lee, I.M. (2008) ‘Lung cancer occurrence in never-smokers: an analysis of 13 cohorts’, Journal of the National Cancer Institute, 100(10), pp.691–699.

Urrutia-Pereira, M., Chatkin, J. M., Chong-Neto, H. J. & Solé, D. (2023) ‘Radon exposure: a major cause of lung cancer in nonsmokers’, Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia, 49(6). 

UNESCAP (2019) ‘Gender Equality and Women’s Empowerment in Asia and the Pacific’, United Nations Economic and Social Commission for Asia and the Pacific [pdf]. <https://www.unescap.org/sites/default/files/publications/B20%20Gender%20Equality%20Report%20v10-3-E.pdf>

UNSCEAR (2006) Effects of Ionizing Radiation, United Nations Scientific Committee on the Effects of Atomic Radiation (New York: United Nations).

Warren G.W. & Cummings, K.M. (2013) ‘Tobacco and lung cancer: risks, trends, and outcomes in patients with cancer’, Am Soc Clin Oncol Educ Book, pp. 359–364.

WHO (2009) ‘WHO Handbook on Indoor Radon: A Public Health Perspective’, World Health Organization [pdf]. <https://iris.who.int/server/api/core/bitstreams/47a93281-8a11-476f-aa7d-5488014ae433/content>

WHO (2014) ‘WHO Guidelines Indoor Air Quality Guidelines: Household Fuel Combustion’, World Health Organization [pdf]. <https://iris.who.int/server/api/core/bitstreams/b7e8337f-bc8b-40fd-af6f-921d7f778ca4/content>

WHO (2021) ‘WHO Global Air Quality Guidelines: PM2.5, PM10, Ozone, Nitrogen Dioxide, Sulfur Dioxide and Carbon Monoxide’, World Health Organization [pdf]. <https://iris.who.int/server/api/core/bitstreams/551b515e-2a32-4e1a-a58c-cdaecd395b19/content>

Xue, Y., Jiang, Y., Jin, S. & Li, Y. (2016) ‘Association between cooking oil fume exposure and lung cancer among Chinese nonsmoking women: a meta-analysis’, Onco Targets Ther, 9, pp.2987–2992. 

Yang, L., Wu, H., Zhao, M., Magnussen, C.G. & Xi, B. (2022) ‘Prevalence and trends in tobacco use, secondhand smoke exposure at home and household solid fuel use among women in 57 low- and middle-income countries, 2000-2018’, Environ Int, 161(107142).

Young, S.C., Chang, L.W., Lee, H.L., Tsai, L.H., Liu, Y.C. & Lin, P. (2010) ‘DNA damages induced by trans, trans-2,4-decadienal (tt-DDE), a component of cooking oil fume, in human bronchial epithelial cells’, Environ Mol Mutagen, 51(4), pp. 315–321.

Zhang, Z. et al. (2012) ‘Indoor Radon concentrations in China: a review’, Radiation Protection Dosimetry, 152(1–3), pp. 144–147.

Zhang, Z.L., Sun, J., Dong, J.Y., Tian, H.L. & Xue, L. (2012) ‘Residential radon and lung cancer risk: an updated meta-analysis of case-control studies’, Asian Pacific Journal of Cancer Prevention, 13(6), pp. 2459–2465.