फायबर-समृद्ध आहाराचा आणि फुफ्फुसांच्या कर्करोगावरील परिणाम

 ५.४. तंतुमय पदार्थांनी समृद्ध आहार

फळे, भाज्या आणि वनस्पतीजन्य पदार्थांमधील काही घटक, जसे की फायबर, हे महत्त्वाच्या गोंधळात टाकणाऱ्या चलांसाठी समायोजन केल्यानंतरही, सिस्टेमिक दाह, लठ्ठपणा आणि मेटाबॉलिक सिंड्रोम कमी करण्याशी संबंधित आहेत [९१].

याव्यतिरिक्त, जास्त फायबरचे सेवन अनेक प्रकारच्या कर्करोगापासून संरक्षण करते असे पूर्वीपासून मानले जात आहे [९२].

या विविध आरोग्य फायद्यांमागील यंत्रणा फायबरमुळे प्रेरित होणाऱ्या आतड्यातील सूक्ष्मजीव आणि चयापचय मार्गांच्या नियमनाशी जोडलेल्या असल्याचे दिसते [९३].

युनायटेड स्टेट्स, युरोप आणि आशियामध्ये केलेल्या अभ्यासांमधील १,४४५,८५० प्रौढांमध्ये, धूम्रपानाची स्थिती, सिगारेटची संख्या आणि फुफ्फुसाच्या कर्करोगाच्या इतर जोखीम घटकांसाठी समायोजन केल्यानंतर, फायबरचे सेवन आणि फुफ्फुसाच्या कर्करोगाचा धोका यांच्यात व्यस्त संबंध आढळला [९४].

त्याचप्रमाणे, मिलर आणि इतरांनी EPIC अभ्यासात समाविष्ट असलेल्या आणि १० युरोपीय देशांमधून भरती केलेल्या ४७८,०२१ व्यक्तींच्या डेटाचा अभ्यास केला, ज्यांनी आहारासंबंधी प्रश्नावली पूर्ण केली होती [९५].

वय, धूम्रपान, उंची, वजन आणि लिंग यासाठी समायोजन केल्यानंतर, फुफ्फुसाच्या कर्करोगाच्या रुग्णांमध्ये फळांचे सेवन आणि फुफ्फुसाच्या कर्करोगाचा धोका यांच्यात एक महत्त्वपूर्ण व्यस्त संबंध आढळला. हा संबंध अभ्यासाच्या सुरुवातीला धूम्रपान करणाऱ्यांमध्ये सर्वात मजबूत होता [९५].

फुफ्फुसाच्या कर्करोगाच्या उपप्रकारांचा विचार करता, बुचनर आणि इतरांनी, २०१० मध्ये, फायबरच्या सेवनामध्ये आणि फुफ्फुसाच्या कर्करोगाच्या धोक्यात व्यस्त संबंध पाहिला, परंतु फुफ्फुसाच्या कर्करोगाच्या विशिष्ट हिस्टोलॉजिकल उपप्रकारांवर कोणताही स्पष्ट परिणाम दिसला नाही [९६].

दुसरीकडे, फायबरच्या वेगवेगळ्या स्रोतांचा विचार करता, ब्रॅडबरी आणि इतरांनी, २०१४ मध्ये नोंदवले की फुफ्फुसाच्या कर्करोगाचा धोका फळांच्या सेवनाशी व्यस्तपणे संबंधित होता, परंतु भाज्यांच्या सेवनाशी संबंधित नव्हता [९७];

तथापि, फळांच्या सेवनाशी असलेला हा संबंध केवळ धूम्रपान करणाऱ्यांपुरता मर्यादित आहे. या डेटानुसार, बुचनर आणि इतरांनी फुफ्फुसाच्या कर्करोगाच्या १८३० नवीन प्रकरणांच्या पाठपुराव्यादरम्यान फळे आणि भाज्यांच्या परिणामांचे विश्लेषण केले; फळे आणि भाज्यांच्या सेवनात दररोज १०० ग्रॅम वाढ केल्याने फुफ्फुसाच्या कर्करोगाचा धोका कमी होतो [९६].

याव्यतिरिक्त, फायबरचे वेगवेगळे स्रोत सकारात्मक परिणाम बदलत नाहीत, जसे की बाल्ड्रिक आणि इतरांनी दाखवून दिले आहे, ज्यांना शेंगांमधून जास्त फायबर असलेल्या आहाराचे सेवन करणाऱ्या माजी/धूम्रपान करणाऱ्यांमध्ये दाहक-विरोधी यंत्रणेद्वारे फायदेशीर परिणाम आढळले [९८]. एकूण फायबरच्या सेवनामध्ये आणि सीओपीडी (COPD) चा धोका कमी होण्यामध्ये एक संबंध आढळून आला आहे, जो सामान्य फुफ्फुसांच्या आरोग्यावर फायदेशीर परिणाम दर्शवतो [99,100].

संदर्भ

Int J Environ Res Public Health. 2021 Mar 1;18(5):2399. doi: 10.3390/ijerph18052399

अन्न, पोषण, शारीरिक क्रियाकलाप आणि मायक्रोबायोटा: फुफ्फुसांच्या कर्करोगावर कोणता परिणाम?

Ersilia Nigro 1,2, Fabio Perrotta 3, Filippo Scialò 2,4, Vito D’Agnano 3, Marta Mallardo 1,2, Andrea Bianco 2,4,*, Aurora Daniele 1,2,*

संपादक: Dagrun Engeset

Ref

Int J Environ Res Public Health. 2021 Mar 1;18(5):2399. doi: 10.3390/ijerph18052399

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Ersilia Nigro 1,2, Fabio Perrotta 3, Filippo Scialò 2,4, Vito D’Agnano 3, Marta Mallardo 1,2, Andrea Bianco 2,4,*, Aurora Daniele 1,2,*

Editor: Dagrun Engeset

Impact of Fiber -Enriched Diet and Lung Cancer

 5.4. Fibers-Enriched Diet

Fruit, vegetables and certain components of

 plant foods, such as fiber, are associated with a reduction in systemic inflammation, obesity and metabolic syndrome, even after adjustment for important confounding variables [91].

 In addition, high fiber intake has long been thought to protect against several types of cancer [92]. 

The mechanisms for those various health benefits seem to be linked to the modulation of the gut microbiota and metabolic pathways that fibers can induce [93].

 Fiber intake is inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors in 1,445,850 adults from studies that were conducted in the United States, Europe, and Asia [94]. 

Similarly, Miller et al. studied data from 478,021 individuals included in the EPIC study, and recruited from 10 European countries and who completed a dietary questionnaire [95]. 

After adjustment for age, smoking, height, weight and gender, there was a significant inverse association between fruit consumption and lung cancer risk in lung cancer patients. The association was strongest among current smokers at baseline [95].

Considering subtypes of lung cancer, Büchner et al., 2010 observed an inverse association between the consumption of fibers and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer [96].

On the other hand, considering different sources of fibers, Bradbury et al., 2014 reported that the risk of cancer of the lung was inversely associated with fruit intake but was not associated with vegetable intake [97]; 

however, this association with fruit intake is restricted to smokers. In accordance with this data, Büchner et al. analyzed the effects of fruits and vegetables during a follow-up of 1830 incident cases of lung cancer; a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk [96]. 

 In addition, different sources of fibers do not alter positive effects, as demonstrated by Baldrick et al. that found beneficial effects in ex/smokers following a diet with high intake of fibers from legumes through anti-inflammatory mechanisms [98].

An association has been also found between total fiber intake and decreased COPD risk suggesting a beneficial impact on general lung health [99,100].

Ref

Int J Environ Res Public Health. 2021 Mar 1;18(5):2399. doi: 10.3390/ijerph18052399

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Ersilia Nigro 1,2, Fabio Perrotta 3, Filippo Scialò 2,4, Vito D’Agnano 3, Marta Mallardo 1,2, Andrea Bianco 2,4,*, Aurora Daniele 1,2,*

Editor: Dagrun Engeset

Effect of Food and dietary Plans on Lung Cancer

 5. Effects of Food and Dietary Plans on Lung Cancer

As said above, body composition and eventually the presence of sarcopenia are crucial factors determining the risk, response to therapy and therefore the prognosis of lung cancer patients. 

Considering nutritional status as a determining factor of the body composition, in recent years growing attention has been paid to the choice of dietary plans as well as to performing physical activity.

 Dietary schemes as well as specific foods-enriched diet influence the predisposition towards cancer disease and the response to therapies and therefore the prognosis. 

The main molecular processes regulated by specific diet patterns, functional foods and physical activity in relation to cancer are the inflammation and oxidative stress. 

In the next paragraphs, we report the main dietary schemes associated to body composition, response to therapy and prognosis of lung cancer patients: caloric restriction, PUFA-enriched diets, Dietary Approaches to Stop Hypertension (DASH), fibers-enriched diet and diary-enriched diet. Since a considerable variety of bioactive ingredients have been identified in foods, we will also report interesting data for single compounds.

5.1. Caloric Restriction

It is widely believed that calorie restriction can extend the lifespan of model organisms and protect against aging-related diseases, such as lung cancer. 

In breast cancer, Simone et al. demonstrated that caloric restriction can augment the effects of radiation therapy as well as chemotherapy in a mouse model of breast cancer [72]. 

Interestingly, Safdie et al. analyzed patients diagnosed with a variety of malignancies (one with lung cancer) that voluntarily fasted prior to (48–140 h) and/or following (5–56 h) chemotherapy reporting a reduction in fatigue, weakness and gastrointestinal side effects while fasting [73]. 

The molecular mechanism of caloric restriction action is mainly related to the decrease of chemotherapy-induced inflammation and induction of energy stress resulting in increased efficacy of therapy. 

In lung cancer, Caiola et al. suggested, through in vitro studies, that caloric restriction regimens may sensitize NSCLC lesions carrying KRAS mutation and LKB1 loss to cytotoxic chemotherapy through induction of energy stress [74]. 

Resveratrol has been proposed as an active molecule mimicking the effects of caloric restriction which may have beneficial effects against numerous diseases such as type 2 diabetes, cardiovascular diseases, and cancer [75]. 

The positive effects in cancer are related to by the inhibition of oxidative stress, inflammation, aging, and fibrosis [76,77].

 In lung cancer, and more widely, in lung diseases resveratrol represents a promising natural compound to be used in association with other drugs [78].

 Although it is clear that resveratrol has shown excellent anti-cancer properties, most of the studies were performed in vitro or in pre-clinical models. Few clinical trials have been developed on the administration of resveratrol in cancer patients [79,80]. 

In addition, resveratrol in its current form is not ideal as therapy because, even at very high doses, it has modest efficacy and many downstream effects [81].

 The identification of the cellular targets responsible for resveratrol effects would help in the development of target specific therapies based on this drug

Ref

Int J Environ Res Public Health. 2021 Mar 1;18(5):2399. doi: 10.3390/ijerph18052399

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Ersilia Nigro 1,2, Fabio Perrotta 3, Filippo Scialò 2,4, Vito D’Agnano 3, Marta Mallardo 1,2, Andrea Bianco 2,4,*, Aurora Daniele 1,2,*

Editor: Dagrun Engeset

Lung cancer Food and Dietary Plans (4)

 4. Food and Dietary Plans in the Prevention/

Control of Lung Cancer

Common phenomena in lung cancer patients are both malnutrition and cancer cachexia [52].

 The prevalence of malnutrition in lung cancer patients ranges from 34.5 to 69%, with the highest incidence in more severe patients and in those undergoing chemotherapies, immunotherapy and/or radiotherapy [53].

 On the other hand, inactivity represents a major risk for loss of functional pulmonary capacities in lung cancer patients [3]. 

Nutritional counselling, planning of meals and use of supplements are essential approaches to counteract malnutrition and sarcopenia in lung cancer. In fact, a nutritional and life-style counselling approach is recommended to control chemotherapy response,

 sarcopenia, prognosis and survival of the lung cancer patients. 

Tanaka et al. (2018) demonstrated that an early nutritional intervention with a dietary counselling in lung cancer patients receiving chemotherapy efficiently counteracts weight loss and sarcopenia [54].

 However, many patients do not achieve recommended dietary intake even after nutritional counselling [55].

 The main nutritional approaches to prevent and

 treat cancer sarcopenia are: an adequate energy intake; an adequate supply of protein for maintenance or gain of muscle; use of supplements.

An adequate protein intake can reduce the incidence and severity of sarcopenia in cancer patients [56].

 It has been demonstrated that a dietary program with energy and protein rich meals and snacks can improve muscle strength and performance status of lung cancer patients [57,58].

The use of supplements in the diet for cancer patients experiencing muscle loss is becoming a very popular approach.

 Several products might be useful in contrasting sarcopenia during cancer (Branched-chain amino acids, carnitine, fish oil,

 Eicosapentaenoic acid (EPA), vitamins and mineral, [59]. Specifically, in lung cancer

, supplementation of diet with EPA and PUFA improves the maintenance of weight and muscle mass in advanced NSCLC patients undergoing chemotherapy as well as physical and cognitive functioning [60,61,62].

Increasing attention has been focused on the possible use of oral ghrelin receptor (G-protein coupled receptor, GHSR-1a) agonists such as anamorelin and HM01 with the aim of exploiting the ghrelin’s orexigenic capacity [63].

 Anamorelin, a ghrelin receptor agonist, has been demonstrated to be able to significantly increase lean body mass [64]. 

Two completed clinical trials (ROMANA1 and 2, NCT01387269 and NCT01387282, respectively), performed on lung patients with inoperable stage III or IV non-small-cell lung cancer and cachexia, demonstrated that anamorelin induces an increase in lean body mass, without modification in the handgrip [65]. A third trial from the same authors, ROMANA3 (NCT01395914) has been completed confirming the improvements in body weight and anorexia-cachexia

 symptoms observed in the original trials, and demonstrating a well toleration to anamorelin administration [66]. 

There are currently two ongoing clinical trials (NCT03743064 and 03743051) investigating the use of anamorelin to treat non-small cell lung cancer-associated weight loss

. Both trials report changes in weight although a definitive result has not been reached. On the contrary, in vitro and vivo data are available about HM01 effects on cachexia but no clinical trials are available yet [67,68].

Regarding the molecular mechanisms underlying anamorelin effects, Garcia and colleagues found the it significantly increases GH, IGF-1 and IGFBP-3 levels with consequent body weight gain [69,70].

 A very recent study compared the two ghrelin receptor agonists anamorelin (non-BBB penetrant) and HM01 (BBB penetrant), demonstrating that HM01

 enhances hypothalamic neuronal activation and increases cumulative food intake compared to ghrelin and anamorelin [71]. The authors also demonstrated that HM01 and anamorelin exert potent effects on calcium mobilization, however anamorelin is potentially more susceptible to treatment-induced tolerance than HM01 due to recruitment of β-arrestin and GHSR-1a internalization [71]

Ref

Int J Environ Res Public Health. 2021 Mar 1;18(5):2399. doi: 10.3390/ijerph18052399

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Ersilia Nigro 1,2, Fabio Perrotta 3, Filippo Scialò 2,4, Vito D’Agnano 3, Marta Mallardo 1,2, Andrea Bianco 2,4,*, Aurora Daniele 1,2,*

Editor: Dagrun Engeset

Lung cancer Impact of Food Nutrtion Microbiota

 Abstract

Lung cancer still represents the leading cause of cancer-related death, globally. Likewise, 

malnutrition and inactivity represent a major risk for loss of functional pulmonary capacities influencing overall lung cancer severity.

 Therefore, the adhesion to an appropriate

 health lifestyle is crucial in the management of lung cancer patients despite the subtype of cancer. 

This review aims to summarize the available knowledge about dietary approaches as well as physical activity as the major factors that decrease the risk towards lung cancer,

 and improve the response to therapies. 

We discuss the most significant dietary schemes positively associated to body composition and prognosis of lung cancer and the main molecular processes regulated by specific diet schemes, functional foods and physical activity, i.e., inflammation and oxidative stress. 

Finally, we report evidence demonstrating that dysbiosis of lung and/or gut microbiome, as well as their interconnection (the gut–lung axis), are strictly related to dietary patterns and regular physical activity playing a

 key role in lung cancer formation and progression, opening to the avenue of modulating the microbiome as coadjuvant therapy. Altogether, the evidence reported in this review highlights the necessity to consider non-pharmacological interventions (nutrition and physical activity) as effective adjunctive strategies in the management of lung cancer.

Ref

Int J Environ Res Public Health. 2021 Mar 1;18(5):2399. doi: 10.3390/ijerph18052399

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Ersilia Nigro 1,2, Fabio Perrotta 3, Filippo Scialò 2,4, Vito D’Agnano 3, Marta Mallardo 1,2, Andrea Bianco 2,4,*, Aurora Daniele 1,2,*

Editor: Dagrun Engeset

Lung cancer Genetic and Racial Disparities

 2.3. Genetic and Racial

 Disparities and Lung Cancer Susceptibility

Lung cancer risk is influenced significantly by

 different racial and ethnic disparities.

 Individuals with African ancestry (AA) have

 higher mortality rates and incidence of lung cancer development at an earlier age compared to individuals with European ancestry (EA) due to disparities in preventive screening monitoring and treatment disparities [39,40].

 In addition, there is a significant disparity in the metabolic pathways and how the body processes nicotine between AA and EA groups, as AA has lower levels of cotinine glucuronidation [41]. 

Non-Hispanic AA males show the highest rates of mortality and lung cancer incidence compared to all race-ethnicities [42,43]. 

Similarly, Primm et al. showed persistent disparities in NSCLC incidence between AA and EA men [44]. 

Interestingly, despite disparities in diagnosis and treatment, AA and Asian NSCLC patients demonstrate better outcomes for the same-stage cancer compared to EA patients [45].

 The cause for disparities is genetic ancestry, as AA populations with LUSC have more genomic instability and aggressive molecular traits, while AA patients with LUAD have a higher frequency of PTPRT and JAK2 gene mutations [46,47].

 Additionally, the Asian population demonstrates a higher frequency of STK11, TP53, and EGFR gene mutation [48],

 but they have longer survival rates and higher chemotherapy responses in comparison to EA patients [49]. 

Ok Another study linked TP53, KRAS, and KEAP1 gene mutations with worse overall survival, whereas EGFR gene mutations are associated with a higher chance of survival [50].

Recent studies found that EA patients have higher mortality rates compared to Hispanics and Asians, and they have a higher susceptibility to lung cancer due to higher frequencies in smoking-related loci [51,52].

 Many studies have revealed racial disparities in the genetic mutation profile of lung cancer patients. Compared to Japanese patients, EA-LUSC patients present a higher frequency of mutations in TP53, PIK3CA, KEAP1, and NFE2L2 genes [53]. 

On the contrary, EA-LUAD patients exhibit a significantly lower occurrence of EGFR mutation but an increased frequency of mutation in the PIK3CA, KEAP1, KRAS, TP53, BRAF, NF1, STK11, RBM10, and MET genes.

 Weiner and Winn reported a higher prevalence

 of EGFR gene mutation in the East Asian population and more predominant KRAS and STK11 gene alterations in EA and AA populations [54]. 

Generally, the disparities in survival rates between EA and AA populations are noticeable in patients who are young and have localized tumors [55].

 The disparities also exist in histological subtype, stage, and tumor grade. Asian or Pacific Islander (API) exhibit a higher frequency of adenocarcinoma (ADC) compared to AA, EA, and American Indian/Alaska Native (AIAN) patients [56].

Ref

International Journal of Molecular Sciences logo

Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur Kratzke

Lung Cancer and Risk Factors

 Ref

International Journal of Molecular Sciences logo

Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur  Kratzke

2.2. Environmental and Lifestyle Risk Factors

Epidemiology and risk factors involve a complex interaction of environmental, genetic mutations, and lifestyle factors that contribute to susceptibility to lung cancer and its outcomes [16,17].

 However, these interactions become more significant when considering ethnic and ancestor differences. 

Although smoking is the predominant cause of lung cancer, another study revealed that 10–25% of all lung cancer patients have never smoked [18].

 This disparity underscores the need to investigate additional risk factors other than smoking, especially in populations where lung cancer is not related to smoking [19].

 Cigarette smoking remains a major risk factor for lung cancer development. The initiation of smoking habits is mediated by peer pressure, family habits, and psychological distress [20,21]. 

Interestingly, Harrell et al. reported that demographic factors such as race, socioeconomic status, and pubertal development were significant predictors of early smoking initiation among schoolchildren [22].

 Additionally, preventative measures for air pollution include techniques like urea-selective catalytic reduction (SCR), diesel particulate filters, and NOx storage-reduction catalysts approved to enhance air quality to avoid additional health effects from gaseous as well as particulate air pollution pollutants [23].

 As a reason, there were substantial declines in lung cancer incidence in the USA from 2007 to 2018. On the other hand, there has been little change in rates among never-smokers, though rates increased significantly in Asian and Pacific Islander populations [24].

 In Denmark, lung cancer trends are influenced by historical smoking patterns, where a decline in male smoking rates led to reduced incidence. In contrast, the prevalence of smoking in women remained stable for longer, contributing to a later increase in lung cancer incidence [25].

 Existing evidence suggests that passive smoke is the cause of a significant proportion of lung cancer in women.

 For instance, Du et al. reported that passive smoking accounts for about 17.9% of lung cancer cases among never-smoking women, most of them exposed to household smoking [26]

. Moreover, a study of Moroccan women showed that 75% of lung cancer cases were recorded in never-smokers, and LUAD was the most common subtype among passive smokers [27].

Zhu et al. reported that non-smoking people who drink tea ≥ 2 cups/day have a greater risk of lung cancer [28]. 

At the population level, cigarette smoking is the primary determinant of the occurrence of lung cancer [29].

 Environmental factors increase the risk of developing lung cancer, such as air pollution, occupational exposure, secondhand smoke, and radiation exposure [30,31].

 In China, a study by Liu et al. observed that occupational environment and meteorological conditions synergistically affect lung cancer development [32]. 

Furthermore, Chinese-style cooking increases lung cancer risk [33].

 Moreover, long-term exposure to air pollutants such as PM2.5, NO2, and NOx significantly increases the risk of developing lung cancer [34]. The World Cancer Research Fund (WCRF) reported that drinking water with high concentrations of arsenic increases lung cancer risk, and the evidence was reported as “convincing” [35]. Additional interaction of these air pollutants with poor lifestyle and high genetic risk dramatically raises the likelihood of lung cancer occurrence [35]. Similarly, Huang et al. showed the same results [36]. However, predicting cancer associated with environmental factors like alcohol consumption and smoking can alter based on the variation in polymorphism of xenobiotic metabolizing enzymes (XME) genes [37]. Pettit et al. studied the genetic correlation between various traits and lung cancer risk, indicating a negative genetic correlation between lung cancer risk and some traits, including dietary behaviors, fitness metrics, educational attainment, and other psychosocial characteristics. On the contrary, the body mass index (BMI) showed a positive genetic correlation with the likelihood of lung cancer [38].

The relationship between lung cancer risk and dietary items like fruits, vegetables, micronutrients, phytochemicals, fat, and beverages has been studied. An increased intake of fruits, vegetables, and carotenoid-rich foods is associated with a reduced risk of developing lung cancer [35].

On the contrary, higher intake of retinol, red meat intake, processed meat intake, alcohol drinking, and dietary fat have been associated with an increased risk of lung cancer. 

However, no link has been reported between the phytochemical “bioflavonoid” and lung cancer risk

Lung cancer Types

 2.1. Histological Subtypes of Lung Cancer

 

Ref

Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur Kratzke

Lung cancer is divided into two major groups: small-cell lung cancer

 (SCLC) and non-small-cell lung cancer (NSCLC).

 SCLC is aggressive and has a high risk for distant metastasis at initial diagnosis [11] and accounts for 12% of all lung cancer cases [12].

 NSCLC is, conversely, the most common group, representing 80% to 85% of the lung cancer cases [13].

 Among the NSCLC, adenocarcinoma (LUAD) is the most common histologic subtype, accounting for 45% of all cases, 

followed by squamous cell carcinoma (LUSC) at 21% of cases, 

while 23% attributed to unclassified histologic subtypes [12]. Notably, LUAD is more common in never-smokes with a predominant EGFR gene mutation, whereas LUSC is more common among smokers with a predominant TP53 gene mutation [14,15].

फुफ्फुसाच्या कर्करोगाचे जीवशास्त्र

 इंट जे मोल सायन्स. २०२५ एप्रिल १७;२६(८):३८१८. doi: १०.३३९०/ijms२६०८३८१८

फुफ्फुसाच्या कर्करोगाचे जीवशास्त्र, जीनोमिक्स आणि वांशिक विषमतेचा सद्यस्थितीतील आराखडा

एनास एस अलसातारी १,२, केली आर स्मिथ १,२, सप्तला पी लोकू गलापथी १,२, एल्बा ए टर्बट-हेरेरा १,२, सांतनु दासगुप्ता १,२,३,*

संपादक: रॉबर्ट आर्थर क्रॅट्झके

Ref

Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur Kratzke

प्रस्तावना

फुफ्फुसाचा कर्करोग हा दुसऱ्या क्रमांकाचा सर्वात सामान्य कर्करोग आहे, ज्याचा घटना दर ११.४% आहे [१].

२०१८ मध्ये युनायटेड स्टेट्समध्ये २,३०,००० हून अधिक नवीन प्रकरणे आढळली, ज्यामुळे स्तन, कोलन आणि प्रोस्टेट कर्करोगासह इतर सर्व कर्करोगांच्या एकत्रित प्रकरणांपेक्षा जास्त मृत्यू झाले [२].

ग्लोबोकॅन २०२० च्या आकडेवारीनुसार, २०२० मध्ये फुफ्फुसाच्या कर्करोगाची अंदाजे २.३ दशलक्ष नवीन प्रकरणे (११.४%) आणि जवळपास १.८ दशलक्ष मृत्यू नोंदवले गेले [३].

आयुष्याच्या पाचव्या दशकापूर्वी फुफ्फुसाचा कर्करोग असामान्य आहे, परंतु वयानुसार त्याचा घटना दर वाढतो [३].

अमेरिकेत, पुरुषांमध्ये फुफ्फुसाच्या कर्करोगाचा घटना दर कमी होत आहे, तर महिलांमध्ये सुरुवातीला वाढ आणि नंतर घट दिसून आली.

हे विशेषतः तरुण स्त्रियांमध्ये अधिक ठळकपणे दिसून येते, ज्यांच्यामध्ये अलीकडे पुरुषांपेक्षा जास्त घटना दर दिसून आले आहेत, विशेषतः नॉन-हिस्पॅनिक श्वेतवर्णीय आणि आशियाई/पॅसिफिक बेटांवरील लोकांमध्ये [४].

त्याचप्रमाणे, नोलेन आणि इतरांच्या एका अभ्यासात असे दिसून आले की, युनायटेड स्टेट्समध्ये तरुण स्त्रियांमध्ये समान वयाच्या पुरुषांपेक्षा फुफ्फुसाच्या कर्करोगाचे प्रमाण जास्त आहे, जे ५०-५४ वयोगटापर्यंत दिसून येते [५].

एका अगदी अलीकडील अभ्यासात असे दिसून आले आहे की फुफ्फुसाच्या कर्करोगाच्या मृत्यू दरातील घट ही घटना दरातील घटीपेक्षा जास्त आहे, विशेषतः पुरुष (वार्षिक ५.०% विरुद्ध २.६%) आणि महिलांमध्ये (वार्षिक ४.३% विरुद्ध १.१%) [६].

दुसरीकडे, विविध वांशिक आणि जातीय गटांमध्ये फुफ्फुसाच्या कर्करोगाच्या घटना दरामध्ये अजूनही विषमता अस्तित्वात आहे। मूळ अमेरिकन लोकांमध्ये या रोगाचे प्रमाण सर्वाधिक आणि घट सर्वात कमी दिसून आली, आणि मिसिसिपी आणि केंटकीसह विविध राज्यांमध्ये, ऐतिहासिक धूम्रपान प्रसारामुळे बहुतेक पाश्चात्य राज्यांपेक्षा दोन ते तीन पट जास्त मृत्यू दर अनुभवला जात आहे [६].

याव्यतिरिक्त, इतर हिस्पॅनिक गटांच्या तुलनेत क्यूबन पुरुषांमध्ये या रोगाचे प्रमाण अधिक आहे, तर अमेरिकेत जन्मलेल्या कृष्णवर्णीय पुरुषांमध्ये कॅरिबियनमध्ये जन्मलेल्या कृष्णवर्णीयांपेक्षा हे प्रमाण जास्त आहे [७].

महिलांमध्ये, अमेरिकेत जन्मलेल्या कृष्णवर्णीय महिलांमध्ये या रोगाचे प्रमाण सर्वाधिक आहे [७].

असे असले तरी, फुफ्फुसाचा कर्करोग हा जगाच्या सर्व भागांमध्ये कर्करोगामुळे होणाऱ्या मृत्यूचे सर्वात सामान्य कारण आहे [८].

२०२० मध्ये, फुफ्फुसाच्या कर्करोगामुळे सुमारे १.८ दशलक्ष मृत्यू झाले, जे सर्व कर्करोगाच्या मृत्यूंपैकी १८% होते.

वय-मानक मृत्यू दर (ASMR) प्रति १,००,००० लोकांमागे १८.० होता (पुरुषांमध्ये २५.९ आणि महिलांमध्ये ११.२) [९,१०].

मृत्यू दरामध्ये प्रादेशिक स्तरावर लक्षणीय फरक दिसून येतो. सर्वाधिक मानवी विकास निर्देशांक (HDI) असलेल्या देशांमध्ये, प्रामुख्याने युरोप आणि उत्तर अमेरिकेत, हे दर सर्वाधिक आहेत, तर उप-सहारा आफ्रिकेत असलेल्या देशांमध्ये हे दर सर्वात कमी आहेत [९].

या समीक्षा लेखात, आम्ही फुफ्फुसाच्या कर्करोगाचे आणि वांशिक विषमतेचे सध्याचे ज्ञान सारांशित केले आहे, ज्यामध्ये जीनोमिक्स, जीवशास्त्र आणि सूक्ष्मजीव परिसंस्था यासह विविध पैलूंवर लक्ष केंद्रित केले आहे.

आम्ही फुफ्फुसाच्या कर्करोगाच्या निर्मितीशी संबंधित भिन्न हिस्टोपॅथॉलॉजिकल आणि आण्विक उपप्रकार, महामारीशास्त्र आणि जोखीम घटक, हिस्टोपॅथॉलॉजिकल आणि आण्विक प्रगतीचे नमुने, केंद्रकीय आणि मायटोकॉन्ड्रियल अनुवांशिक बदल, एपिजेनेटिक बदल, रोगप्रतिकार प्रणालीतील बिघाड आणि मायक्रोबायोममधील असंतुलन देखील सादर केले आहेत.

Roadmap of lung cancer Biology (Introduction)

 Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur Kratzke

Introduction

Lung cancer ranks as the second most prevalent malignancy, with an 11.4% incidence rate [1]. 

Over 230,000 new cases were detected in the United States in 2018, leading to more fatalities than all other cancers including breast, colon, and prostate cancer combined [2].

 According to GLOBOCAN 2020 data, approximately 2.3 million new cases (11.4%) and almost 1.8 million deaths from lung cancer were recorded in 2020 [3].

 Lung cancer is uncommon before the fifth decade of life, but its incidence rises with age [3].

 In the U.S., lung cancer incidence among males continues to decline, while females showed an initial increase followed by a decline.

 It is particularly marked among younger women who have recently demonstrated higher incidence rates than males, notably for non-Hispanic Whites and Asians/Pacific Islanders [4].

 Similarly, a study by Nolen et al. reported higher rates of lung cancer in the United States in young women than men of similar age, extending to those aged 50–54 [5].

 A very recent study showed reductions in lung cancer mortality rates that have exceeded reductions in incidence, particularly among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually) [6]. 

On the other hand, the disparity in lung cancer incidence still exists among various racial and ethnic groups. 

The highest incidence rates and the slowest decline were seen in Native Americans, with various States, including Mississippi and Kentucky, continuing to experience mortality rates two to three times higher than most Western States due to historic smoking prevalence [6]. 

In addition, Cuban males show higher incidence rates among other Hispanic groups, whereas U.S.-born Black males show higher incidence rates than Caribbean-born Blacks [7].

 Among females, US-born Blacks exhibit the highest incidence rates [7]. 

Nevertheless, lung cancer is the most common cause of cancer-related death in all parts of the world [8]. 

In 2020, lung cancer was responsible for around 1.8 million deaths, accounting for 18% of all cancer deaths.

 The age-standardized mortality rate (ASMR) was 18.0 per 100,000 (25.9 in men and 11.2 in women) [9,10].

 Mortality exhibits substantial regional variation. The highest rates are seen in countries with high Human Development Index (HDI) scores, primarily from Europe and North America, while the lowest rates are noted among those mainly located in Sub-Saharan Africa [9].

In this review article, we summarize the current knowledge of lung cancer and racial disparities, focusing on various aspects, including genomics, biology, and microbial landscapes. 

We also presented divergent histopathological and molecular subtypes, epidemiology and risk factors, histopathological and molecular progression patterns, nuclear and mitochondrial genetic alterations, epigenetic alteration, immune system dysfunction, and microbiome dysbiosis associated with lung tumorigenesis.

Lung Cancer Introduction

 Introduction

Lung. Cancer Introduction

Extracellular vesicles (EVs) are lipid bilayer-enclosed extracellular structures which can be formed by outward budding of the plasma membrane or by an intracellular endocytic trafficking pathway involving fusion of multivesicular late endocytic compartments with the plasma membrane. 

These fusion events result in the extracellular release of the intraluminal vesicles of these compartments, generating a subtype of EVs termed ‘exosomes’ [1]. 

Information transmission between tumor cells and various cells in the microenvironment plays an important role in tumor metastasis, and exosomes are one of the important mediums of intercell communication [1, 2].

 Exosomes are vesicles with a diameter of 30–100 nm secreted by different types of cells [3]. 

They carry many kinds of substances, such as lipids, nucleic acids, and proteins, and are widely distributed in body fluids, including urine, plasma, lavage fluid, serosal effusion, and cerebrospinal fluid [4].

 Exosomes have important roles in multiple physiological and pathological processes, exerting biological functions. On the one hand, they are necessary to maintain normal physiological responses. On the other hand, in the pathological state, especially in the tumor environment, they promote carcinogenesis, proliferation, migration, invasion, immunosuppression, and angiogenesis as well as reshape the microenvironment [5].

In recent years, the study of exosomes in tumor has received enormous interest.

 Exosomes contain bio-macromolecules to participate in information exchange between cells [6]. 

They can increase the invasion ability of tumor cells and promote tumor metastasis, which has become a research hotspot in the field of cancer recently [7, 8]. 

Different types of tumor cells secrete different exosome contents. Additionally, factors affecting cell homeostasis, such as a hypoxic microenvironment, survival pressure, and chemotherapy drugs, induces tumor cells to secrete exosomes [9, 10]. 

Therefore, the volume of exosomes secreted by tumors is much higher than that of normal cells. Although the role of most exosomal compounds in cancer is unclear, previous studies have shown that tumor-derived exosomes promote tumor growth and metastasis by inducing epithelial–mesenchymal transformation (EMT) of tumor cells.

 They also promote angiogenesis, the transformation of cancer-associated fibroblasts, immunosuppression, and formation of a premetastatic microenvironment by acting on stromal cells in the microenvironment [11–15].

Several studies have shown that differential expression of exosome contents is closely related to lung cancer metastasis, playing an important role in the multilink and multistep process [16, 17].

 The multiple mechanisms of tumor-derived exosomes promoting cancer metastasis are mainly summarized in Fig. 1.

 The abscission of cancer cells is essentially a manifestation of increased migration and invasion of tumor cells. Compared with those in healthy people, exosomes are more abundant in circulating body fluids of patients with lung cancer. 

A number of studies have found that exosomes promote the occurrence and development of lung cancer by promoting the formation of the lung cancer microenvironment, 

increasing the ability of tumor cell invasion and metastasis, mediating tumor immunosuppression, and participating in chemo-radiotherapy resistance [18].

 The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Therefore, in this article, the relevant research status of the role of exosomes in lung cancer migration and invasion, immunosuppression and escape, angiogenesis, and other processes is reviewed.

Fig. 1.

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Tumor-derived exosomes promote cancer metastasis. Tumor-derived exosomes through multiple mechanisms participate in cancer metastasis by reshaping the tumor microenvironment; promoting cellular epithelial–mesenchymal transformation (EMT); promoting cell proliferation, inhabiting apoptosis; immunosuppression; promoting hematogenous metastasis and angiogenesis of metastasitic tumor to promote cancer metastasis

Ref

Mol Cancer. 2021 Sep 13;20:117. doi: 10.1186/s12943-021-01411-w

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms

Chunyang Jiang 1,✉, Na Zhang 2, Xiaoli Hu 3, Hongyan Wang 4,✉

Lung cancer (Tumour exosomes ,,Metastasis)

 

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms 

 Metastasis is the spread of cancer cells from their original location to other parts of the body. 

Exosomes are 40–160 nm extracellular vesicles produced by cancer cells (tumor-derived exosomes) that facilitate tumor progression, metastasis, angiogenesis, and immune evasion. 

Angiogenesis is the physiological process of forming new capillary blood vessels from pre-existing vasculature, 

Abstract

As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. 

Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. 

Lung cancer is a major malignant tumor that seriously threatens human health.

 The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis.

 Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. 

By promoting epithelial–mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. 

This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application.

 In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. 

Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in th,✉,✉e near future.

Ref

. 2021 Sep 13;20:117. doi: 10.1186/s12943-021-01411-w

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms

Chunyang Jiang ^1,✉, Na Zhang ², Xiaoli Hu ³, Hongyan Wang ^4,✉

 वायु प्रदूषण आणि फुफ्फुसांचा कर्करोग

संदर्भ

Curr Environ Health Rep. 2023 Dec 6;10(4):478–489. doi: 10.1007/s40572-023-00421-8

वायु प्रदूषण आणि फुफ्फुसांचा कर्करोग: रोगजनक यंत्रणा आणि क्लिनिकल उपयुक्तता म्हणून एक्स्ट्रासेल्युलर वेसिकल्सचे योगदान

जोनाथन गोन्झालेझ-रुइझ १, अँड्रिया ए. बकारेली २, डेव्हिड कांतू-डी-लिओन १, डिडियर प्राडा ३

प्रस्तावना

अलीकडच्या वर्षांत, मानवी आरोग्यावर वायुप्रदूषणाचे होणारे प्रतिकूल परिणाम जगभरात चिंतेचा विषय बनले आहेत [१, २].

आपण श्वास घेत असलेल्या हवेची गुणवत्ता आपले आरोग्य राखण्यात, विशेषतः फुफ्फुसांच्या आरोग्याच्या बाबतीत, महत्त्वपूर्ण भूमिका बजावते [३].

वायुप्रदूषकांना दीर्घकाळ संपर्क आल्याने खोकला, घरघर, श्वास लागणे आणि छातीत घट्टपणा यांसारखी विविध प्रकारची श्वसन लक्षणे दिसू शकतात, जी सर्व तीव्र आणि दीर्घकालीन परिणामांशी संबंधित आहेत [४].

हानिकारक कण आणि वायूंच्या जटिल मिश्रणाने बनलेल्या वायुप्रदूषकांचा संबंध दमा, क्रॉनिक ऑब्स्ट्रक्टिव्ह पल्मोनरी डिसीज (COPD), फुफ्फुसांची कार्यक्षमता कमी होणे आणि फुफ्फुसांचा कर्करोग यासह विविध प्रकारच्या श्वसन विकारांशी जोडला गेला आहे,

विशेषतः, नॉन-स्मॉल सेल लंग कॅन्सर (NSCLC) [५]. पर्यावरणीय वायुप्रदूषक आणि फुफ्फुसांचा कर्करोग यांच्यातील संबंधाचा सखोल अभ्यास करण्यात आला आहे [३].

ऑक्टोबर २०१३ मध्ये, जागतिक आरोग्य संघटनेच्या कर्करोगावरील विशेष संस्थेने, म्हणजेच इंटरनॅशनल एजन्सी फॉर रिसर्च ऑन कॅन्सर (IARC) ने जाहीर केले की बाह्य वायू प्रदूषण मानवांसाठी कर्करोगजन्य (गट १) म्हणून वर्गीकृत केले गेले आहे [६].

पुढील महामारीविज्ञान अभ्यासांनी वायू प्रदूषकांच्या दीर्घकाळ संपर्कात राहणे आणि फुफ्फुसाच्या कर्करोगाचा विकास यांच्यात एक मजबूत संबंध सातत्याने दर्शविला आहे [७].

फुफ्फुसाचा कर्करोग हा सर्वात प्रचलित कर्करोग आहे आणि तो कर्करोगाशी संबंधित मृत्यूंचे प्रमुख कारण आहे, तसेच ही एक महत्त्वपूर्ण जागतिक आरोग्य समस्या आहे,

ज्याची व्याप्ती सध्याची जागतिक आकडेवारी दर्शवते. जगभरात, फुफ्फुसाचा कर्करोग हा सर्वात सामान्य कर्करोग आहे आणि त्याचा प्रभाव लक्षणीय आहे.

२०२२ मध्ये, फुफ्फुसाच्या कर्करोगाची २० लाखांहून अधिक नवीन प्रकरणे नोंदवली गेली, जी सर्व नवीन कर्करोगाच्या निदानांपैकी अंदाजे ११% होती [८].

g in the lungs [23].वायू प्रदूषणाच्या वायूंमध्ये नायट्रोजन ऑक्साईड (NOx: NO आणि NO2) आणि सल्फर डायऑक्साइड (SO2) यांचा समावेश होतो, जे प्रामुख्याने ज्वलन प्रक्रियेतून तयार होतात, जसे की वाहनांच्या इंजिनमध्ये, ऊर्जा प्रकल्पांमध्ये आणि औद्योगिक सुविधांमध्ये [24]. हे प्रदूषक वातावरणातील इतर संयुगांशी अभिक्रिया करून नायट्रिक ॲसिड (HNO3) आणि ओझोन (O3) सारखे दुय्यम प्रदूषक तयार करू शकतात [25].

अभ्यासातून असे दिसून आले आहे की, नायट्रोजन ऑक्साईडच्या संपर्कात आल्याने, विशेषतः इतर प्रदूषकांसोबत, फुफ्फुसाच्या कर्करोगाचा धोका वाढतो [26].

O3, जो प्रकाशरासायनिक धुराचा एक प्रमुख घटक आहे, हे आणखी एक महत्त्वाचे वायू प्रदूषक आहे जे सूर्यप्रकाशाच्या उपस्थितीत नायट्रोजन ऑक्साईडची अस्थिर सेंद्रिय संयुगांशी (VOCs) अभिक्रिया होऊन तयार होते [27].

ओझोनच्या दीर्घकाळ संपर्कात राहण्याचा संबंध श्वसनसंस्थेवरील प्रतिकूल परिणामांशी जोडला गेला आहे, आणि अलीकडील संशोधनात ओझोनच्या संपर्कात येणे आणि फुफ्फुसाच्या कर्करोगाचा विकास यांच्यात संभाव्य संबंध असल्याचेही सूचित केले आहे [28].

अस्थिर सेंद्रिय संयुगे देखील वायू प्रदूषणात उपस्थित असतात आणि ती औद्योगिक प्रक्रिया, वाहनांमधून होणारे उत्सर्जन आणि विद्रावक (solvents) यासह विविध स्रोतांमधून उत्सर्जित होतात [29].

बेंझिन, फॉर्मल्डिहाइड आणि 1,3-ब्युटाडाइन यांसारख्या काही VOCs चे IARC द्वारे कर्करोगजन्य पदार्थ म्हणून वर्गीकरण केले गेले आहे [30].

ही सर्व प्रदूषके पेशी आणि ऊतींमध्ये स्वतंत्रपणे तसेच मिश्रणाच्या स्वरूपात कार्य करू शकतात. त्यामुळे, वायू प्रदूषणामध्ये विविध संयुगांचा समावेश असतो, जी दीर्घकाळ संपर्कात राहिल्यास फुफ्फुसाच्या कर्करोगाचा, विशेषतः नॉन-स्मॉल सेल फुफ्फुसाच्या कर्करोगाचा (NSCLC) धोका वाढण्यास हातभार लावू शकतात [31].

वायू प्रदूषण आणि फुफ्फुसाच्या कर्करोगाचा विकास: नुकसानीच्या संभाव्य यंत्रणा आणि EVs चे महत्त्व

फुफ्फुसाच्या कर्करोगास कारणीभूत ठरू शकणाऱ्या अनेक यंत्रणा वायू प्रदूषकांमुळे, स्वतंत्रपणे आणि मिश्रणाच्या स्वरूपात, सक्रिय होतात.

फुफ्फुसाच्या कर्करोगास हातभार लावणाऱ्या सर्वात अभ्यासलेल्या घटकांमध्ये कमी-तीव्रतेची, दीर्घकालीन जळजळ, ऑक्सिडेटिव्ह ताण, थेट उत्परिवर्तन, एपिजेनेटिक बदल आणि माइटोकॉन्ड्रियल व एंडोथेलियल बिघड यांचा समावेश आहे, परंतु इतरही अनेक घटक आहेत. EVs यापैकी काही यंत्रणांमध्ये योगदान देऊन इतर पेशींपर्यंत संकेत पोहोचवू शकतात आणि वायू प्रदूषणाच्या नुकसानीशी जुळवून घेण्यासही मदत करू शकतात. वायू प्रदूषण-संबंधित नुकसान आणि EVs च्या भूमिकेचा सारांश आकृती 1 मध्ये दर्शविला आहे

.

Air pollution and Lung Cancer

Ref

Curr Environ Health Rep. 2023 Dec 6;10(4):478–489. doi: 10.1007/s40572-023-00421-8

Air Pollution and Lung Cancer: Contributions of 

Extracellular Vesicles as Pathogenic Mechanisms and Clinical Utility

Jonathan González-Ruíz 1, Andrea ABaccarelli 2, David Cantu-de-Leon 1, Diddier Prada3

Introduction

In recent years, the adverse effects of air pollution on human health have become a growing concern worldwide [1, 2]. 

The quality of the air we breathe plays a crucial role in maintaining our well-being, particularly when it comes to lung health [3]. 

Prolonged exposure to air pollutants may induce a wide range of respiratory symptoms, including coughing, wheezing, shortness of breath, and chest tightness, all of them linked with acute and long-term effects [4].

 Air pollutants, consisting of a complex mixture of harmful particles and gases, have been linked to a wide range of respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), reduced lung function, and lung cancer,

 in particular, non-small cell lung cancer (NSCLC) [5]. The association between environmental air pollutants and lung cancer has been extensively studied [3].

 In October 2013, the specialized cancer agency of the World Health Organization, the International Agency for Research on Cancer (IARC) announced that outdoor air pollution was classified as carcinogenic to humans (Group 1) [6].

 Further epidemiological studies have consistently demonstrated a strong link between prolonged exposure to air pollutants and the development of lung cancer [7].

Lung cancer ranks as the most prevalent cancer and remains the primary cause of cancer-related deaths and is a significant global health issue,

 with current worldwide statistics reflecting its magnitude. Across the globe, lung cancer stands as the most common cancer, and its impact is substantial.

 In 2022, there were over 2 million new cases of lung cancer reported, accounting for approximately 11% of all new cancer diagnoses [8].

 Unfortunately, lung cancer continues to be the leading cause of cancer-related deaths globally. While this cancer affects both men and women, the statistics reveal significant sex disparities.

 Among men, lung cancer remains the leading cause of cancer-related mortality. 

Among women, it ranks second only to breast cancer, being a major cause of mortality among them.

 These statistics underscore the importance of understanding both the overall prevalence of lung cancer and the gender-specific differences in its incidence and consequences [9].

 It is also the third most common cancer, following breast and colorectal cancers, and the second leading cause of cancer death after breast cancer among women vulnerable groups around the world include individuals with limited access to healthcare, low socioeconomic status, heavy tobacco user, and those living in highly polluted areas [10].

Air pollution may activate several cellular, molecular, and systemic changes, including inflammation, oxidative damage, microthrombosis, epigenomic changes, and activation of several other cellular responses, including the release of extracellular vesicles (EVs) [11••].

 EVs encompass a heterogeneous group of vesicles that can be classified into three main subtypes, microvesicles, exosomes, and apoptotic bodies [12].

 EVs are membrane-bound structures that are shed from the plasma membrane of cells [13]. They encapsulate a diverse range of molecules, including peptides, nucleic acids (such as microRNAs, mRNAs, and long noncoding RNAs), lipids, and metabolites. This cargo can be transferred to recipient cells, modulating their function and behavior [14].

 In normal cells, EVs play an important role in intercellular communication by allowing cells to exchange information and signals with each other [15]. EVs have been shown to be involved in a variety of physiological and pathological processes, including immune regulation, tissue repair and regeneration, inflammation, and angiogenesis [16]. EVs can be released practically by any cell, including cancer cells [17], and have been implicated in tumor growth, metastasis, and drug resistance [18]. This review examines the mechanisms of air pollution’s impact on lung cancer development, with a focus on the contribution of extracellular vesicles to carcinogenesis and cancer progression. Additionally, it explores the potential utility of these vesicles in clinical settings for lung cancer (i.e., NSCLC).

Air Pollution and Its Impact on Human Health

Air pollution components contain particulate matter (PM) and gases, including volatile organic compounds. 

Particulate matter is a common component of air pollution and consists of tiny particles suspended in the air [19].

 These particles can be classified based on their size, with particles with a diameter of 2.5 µm or less (PM2.5) and PM10 (10 µm or less), also called coarse particles, and ultrafine particles (PM0.1), all of them being studied in 

relation to lung cancer [20].

 PM2.5 can penetrate deep into the respiratory system, reaching the lungs’ alveolar regions [21]. 

Inhaled fine PM deposited on the surface of the airways may either stay intact or partially dissolve but can also be cleared by mucociliary clearance and phagocytosis [22]

. PM can carry various carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals, and organic compounds, which have been linked to cancer development, including in the lungs [23].

 Air pollution gases include nitrogen oxides (NOx: NO and NO2) and sulfur dioxide (SO2), which are produced primarily from combustion processes, such as those occurring in vehicle engines, power plants, and industrial facilities [24]. These pollutants can react with other compounds in the atmosphere to form secondary pollutants, such as nitric acid (HNO3) and ozone (O3) [25].

 Studies have shown that exposure to nitrogen oxides, particularly in combination with other pollutants, increases the risk of lung cancer [26].

 O3, a key component of photochemical smog, is another important air pollutant formed by the reaction of nitrogen oxides with volatile organic compounds (VOCs) in the presence of sunlight [27].

 Prolonged exposure to ozone has been associated with adverse respiratory effects, and recent research also indicates a potential link between ozone exposure and lung cancer development [28]. 

Volatile organic compounds are also present in air pollution and are emitted from a wide range of sources, including industrial processes, vehicle emissions, and solvents [29].

 Some VOCs, such as benzene, formaldehyde, and 1,3-butadiene, have been classified as carcinogens by the IARC [30]. 

All these pollutants may act in cells and tissues individually but also as mixtures. Therefore, air pollution includes a variety of compounds that, after long-term exposure, can contribute to an increased risk of developing lung cancer, particularly non-small cell lung cancer (NSCLC) [31].

Air Pollution and the Development of Lung Cancer: Potential Mechanisms of Damage and Relevance of EVs

Several mechanisms that could lead to lung carcinogenesis are activated by air pollutants, individually and as mixtures. 

The most studied factors contributing to lung carcinogenesis include low-grade, chronic inflammation, oxidative stress, direct mutagenesis, epigenetic changes, and mitochondrial and endothelial dysfunction, but there are many others. EVs can contribute to some of these mechanisms to carry on signals to other cells and even contribute to adapting to air pollution damage. A summary of air pollution-related damage and the role

 of EVs is shown in Fig. 1.

Fig. 1.

 The fig shores pathway of air pollutants malignant tumouurs and metastasis

Conclusions 

Addressing the impact of ambient air pollutants on lung health is highly relevant due to the adverse effects these pollutants have on respiratory symptoms,

 lung function, and the development of lung cancer [121••]. This risk is more prominent in a climate change context with an increased number of wildfires worldwide [122].

 The link between air pollutants and lung cancer is now well-established, with particulate matter, NOx, PM2.5, and volatile organic compounds being key contributors [26, 121••].

 These pollutants can carry direct carcinogens and induce systemic, long-term inflammation, and oxidative stress in the lung cells, leading to DNA damage, mutations, epigenetic changes, the release of EVs, and the promotion of tumor growth and progression [59, 123]. Inflammatory signaling pathways, sometimes modulated by EVs, facilitate a tumor-promoting microenvironment that supports the development of lung cancer [124•].

 Effective strategies and interventions to mitigate the harmful effects of air pollutants, including developing biomonitoring of these interventions, which could include EV and EV-cargo, on lung health are needed [125•]

. By addressing air pollution exposures in multiple ways (e.g., promoting clean energy sources, improving industrial practices with stricter emission standards, mandating and incentivizing stricter fuel efficiency standards for vehicles, strengthening air quality standards and regulations, reduce deforestation),

 we can protect public health and improve outcomes for individuals affected by air pollution-related lung cancer [121••, 126].

 EVs are critical components of liquid biopsy that will revolutionize medical follow-up in clinical oncology, especially in lung cancer, analyzing not only their number but their composition (miRNAs, lncRNAs, metabolites, peptides) and understanding tumor phenotypes in plasma without needing access to the tumors directly [127].

   

Tobacco Cessation in Lung cancer

 3.6. The Importance of Tobacco Cessation

Tobacco is a known cause of various types of tumors, accounting for approximately 85% of lung cancer cases and 30% of cancer mortality [84].

Optimizing smoking cessation services within an LDCT lung cancer screening program has the potential to improve the cost-effectiveness and the overall efficacy [85].

However, there is limited evidence regarding the optimal design and integration of tobacco cessation services.

A personalized intervention booklet, utilizing LDCT scan images, has been developed for delivery by trained smoking cessation practitioners. The results highlight the benefits of co-development during intervention creation and emphasize the need for further evaluating its effectiveness [86].

In a study by Park et al. [86], the impact of counseling using the 5As approach (Ask about smoking, Advise to quit, Assess readiness to quit, Assist with tobacco dependence treatment, and Arrange follow-up) on smoking cessation was evaluated. The study focused on a subset of smokers enrolled in the National Lung Screening Trial (NLST). The results showed that the “assist” and “arrange” steps of 5As counseling were associated with increased odds of quitting at 12 months.

In a study by Bade et al. [87], smoking cessation rates were compared between patients who underwent LDCT screening and those who did not. The study revealed higher smoking cessation rates among patients who attended counseling sessions in the LDCT screening group at 12 months (14.6%) and 24 months (12.9%) compared to those who did not attend counseling (12 months: 6.7%, 24 months: 7.6%, p-values from the analysis: p < 0.0001 and p = 0.002, respectively).

In order to be effective, lung cancer screening requires a multidisciplinary approach, encompassing individualized risk assessment, shared decision making, smoking cessation, structured reporting, high-quality multi-specialty cancer care, and reliable follow-up. Specialized organizations have outlined the key components and metrics that screening programs should incorporate. Ongoing research focuses on long-term outcomes, the refinement of screening criteria, and the use of biomarkers for early cancer detection [88].

A quasi-experimental study by Luh et al. examined a screening program emphasizing primary prevention by encouraging smoking cessation [89]. The study found that patients who received counseling from physicians and nurses showed greater odds of advancing in terms of readiness to quit compared to a control group (OR 2.27, 95% CI 1.07–4.84), while patients who received a smoking cessation leaflet had no significant difference (OR 0.99, 95% CI 0.44–2.25). [90].

Zeliadt et al. conducted a pilot feasibility trial to evaluate the impact of proactive outreach telephone counseling on behavioral cessation support and quit rates [90]. The study showed that patients who received the intervention had higher rates of using behavioral cessation support programs than the control group (44% vs. 11%, RR 4.1, 95% CI 1.7–9.9).

Lung cancer screening could prompt current smokers to reflect on their health and might present an opportunity to engage them in discussions about smoking cessation.

Ref

Healthcare (Basel). 2023 Jul 21;11(14):2085. doi: 10.3390/healthcare11142085

Systematic Review of Lung Cancer Screening: Advancements and Strategies for Implementation

Daniela Amicizia 1,2, Maria Francesca Piazza 1,*, Francesca Marchini 1, Matteo Astengo 1, Federico Grammatico 1,2, Alberto Battaglini 1, Irene Schenone 1, Camilla Sticchi 1, Rosa Lavieri 1, Bruno Di Silverio 1, Giovanni Battista Andreoli 1, Filippo Ansaldi 1,2

Editor: Clara Benna

Lung Cancer conclusions

 Conclusions

Risk factors for lung cancer have been mostly understood and well characterized. Primary prevention of this disease therefore 

seems to be easy to implement by eliminating environmental hazards and smoking.

 Despite this, lung cancer remains the leading cause of death among malignant cancers in all highly developed countries. The causes of this

 phenomenon should be sought in the growing problem of environmental pollution,

 but above all in the difficulty of eliminating the addiction to smoking. In the prevention of lung cancer, the basic factor is not smoking. 

Tobacco smoke is the most common cause of lung cancer. It is worth noting that electronic cigarettes are also not recommended in the context of prevention. The lack of proper education means that young people continue to reach for nicotine-containing products, first e-cigarettes and then traditional cigarettes. However, nicotine addiction is extremely strong in many people, and eliminating the addiction using traditional methods (psychotherapy, nicotine replacement therapy, pharmacotherapy) turns out to be impossible. In such cases, reducing the health risk associated with smoking cigarettes can be achieved by replacing them with smokeless products containing nicotine. Many scientific studies have shown that aerosols from e-cigarettes and tobacco heating devices contain over 90% less carcinogenic substances than cigarette smoke [145].

However, it should be remembered that while the composition of the aerosol is known in tobacco heating devices, in the case of e-liquids, it can be modified by the owners of e-cigarettes or the companies producing them (this has been the cause of many cases of acute lung injury in people using e-liquids containing THC and vitamin E acetate). Therefore, in many countries (USA, the Netherlands, Belgium, Germany), HnB devices have been defined as products with a reduced health risk compared to traditional cigarettes, and international experts issue cautious recommendations on the possibility of reducing the health risk in cigarette smokers by replacing them with tobacco heating products [146].

It has been proven that proper nutrition, with particular emphasis on vegetables and fruits, as well as regular physical activity have a positive effect on reducing the risk of lung cancer [147].

Preventive programs are also being carried out for people who are potentially at risk of developing this type of cancer. The screening test involves performing a low-dose computed tomography scan to detect lung cancer at an early stage [148].

To sum up, the vast majority of lung cancer

 cases are the result of inhalation of substances that promote their formation, e.g., tobacco smoke, car exhaust fumes and smoke from burning coal. Proper prevention of lung cancer and reduction

 in exposure to carcinogens increase the chance of staying healthy.

Ref

Int J Mol Sci. 2025 Feb 26;26(5):2049. doi: 10.3390/ijms26052049

Lung Cancer—Epidemiology, Pathogenesis, Treatment and

 Molecular Aspect of literature 

 Beata Smolarz 1,*, Honorata Ł

ukasiewicz 2, Dariusz Samulak 3,4, Ewa Piekarska 5, Radosław Kołaciński 5, Hanna Romanowicz 1

Editor: Verena Trett

Lung cancer Risk Factors

 8. Risk Factors

The most important risk factor for lung cancer is smoking, primarily active smoking, but there is objective 

evidence that passive smoking is also important. Smoking is the cause of 80–90% of lung cancer cases, and the lifetime risk of developing lung cancer among male smokers is about 17%, among smoking women is about 12%, and among non-smokers is about 1.5% [36,78].

The literature emphasizes the higher risk of lung cancer in people with long-term exposure to compounds such as radon, asbestos, polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, silicone, vinyl chloride, nickel and chromium compounds and diesel engine exhaust [79,80].

 The compounds mentioned above are characterized by a high genotoxic potential, which contributes to the formation of numerous oxidative and nitrative damages.

 In addition, multidirectional activation of signal transduction pathways is observed, as well as the production of the “cross-talk” phenomenon, which leads to an increase in uncontrolled cellular proliferation [81]. 

Exposure of the lung area to ionizing radiation applied for other cancers (e.g., early Hodgkin lymphoma or breast cancer) as well as environmental pollution also increases the risk of lung cancer [36].

 The occurrence of lung cancer in first-degree relatives is associated with a higher risk of developing the disease than in the general population [82,83].

Lung cancer is most often caused by smoking, but in some patients, it is associated with genetic predisposition, according to a study published by the American Society of Clinical Oncology (ASCO).

 American specialists have shown that the same predisposition can cause other types of cancer in patients with lung cancer, such as pancreatic cancer, ovarian cancer in women and prostate cancer in men. 

They warn that the patient’s closest relatives may also be at greater risk of cancer. 

Experts from the American Society of Clinical Oncology point out that most lung cancers can be associated with cigarette smoking, as well as other environmental factors, such as exposure to asbestos, but in the case of thousands of patients, the development of this disease is driven by inherited genetic factors.

 Until now, it seemed that adverse genetic changes conducive to lung cancer could be caused by adverse environmental factors, as well as improper lifestyle, including, above all, smoking. However, some people have inherited genetic changes that predispose them more to this cancer. 

Research by American specialists shows that the detection of inherited genetic changes (pathogenic germline variants—PGV) is therefore of great importance in predicting the risk of lung cancer.

 It has been established that it occurs in a fairly large group, 15% of patients with lung cancer. This is also important information for the closest relatives of these patients. 

Early detection of genetic predisposition allows one to reduce the risk of this disease, as well as detect it early, when even more effective treatment is possible [84]. 

The study included 7788 patients with lung cancer, among whom 1161 patients were found to have inherited genetic changes in 81 known cancer mutations so far. 

Approximately 95.1% of patients with these lesions could be treated with available therapies or could be covered by early detection of the disease ,(84)

Fig 6 Risk factors

Smoking

 Smoking is the cause of 90% of lung cancer cases in men and 80% in women. Smokers have a 30 times higher risk of death from lung cancer than non-smokers. Cigarette smoke hides over 7000 chemical compounds, including over 70 compounds considered carcinogenic.

Secondhand smoke is also associated with a higher risk of lung cancer compared to people who are not exposed to tobacco smoke. It is estimated that about 20–50% of “non-smokers” who suffer from lung cancer are passive smokers [85].

Alcohol

alcohol Studies indicate that people who abused alcohol were more likely to develop lung cancer.

 Researchers do not provide exact data but estimate that it may be related to another factor: smoking. Studies show that people are more likely to reach for cigarettes when they drink.

 Researchers at the University of Liverpool studied 125,249 British drinkers and 47,967 Americans. As many as six genes have been identified that, in their opinion, are associated with excessive alcohol consumption and, consequently, with lung cancer [86].

Genetic predisposition

genetic predisposition The role of genetic factors is still quite poorly understood. The high incidence of lung cancer 

in some families is associated with a genetically determined tendency to overactivate carcinogenic compounds contained in tobacco smoke or to remove these compounds from the body too slowly. A tendency to slowly repair DNA damage in respiratory epithelial cells after the action of carcinogens is also inherited. To sum up, it can be stated that the hereditary condition is primarily a special susceptibility to the carcinogenic effects of tobacco. This inheritance is the result of the presence of polymorphisms (population variants) in many genes, and there are currently no reliable genetic tests to determine the high risk of developing lung cancer.

Research by American specialists shows that the detection of inherited genetic changes (pathogenic germline variants—PGV) is of great importance in predicting the risk of lung cancer. It has been established that it occurs in a fairly large group, i.e., 15% of patients with lung cancer [84].

Occupational factors

occupational factors Exposure to many occupational factors has consequences in the form of the development of lung diseases, including lung cancer. The most important occupational carcinogens include asbestos, silica, heavy metals and polycyclic aromatic hydrocarbons [87]. All forms of asbestos (chrysotile and amphiboles, including crocidolite, amosite and tremolite) are carcinogenic, although the potency of chrysotile is less than that of other types, likely due to its more effective removal from the lungs. In many underdeveloped countries, occupational exposure to asbestos remains widespread [87,88].

Elevated risk of lung cancer has been reported in several industries and occupations associated with exposure to polycyclic aromatic hydrocarbons, such as aluminum production, coal gasification, coke production, iron and steel foundries, tar distillation, roofing and chimney cleaning. It has also been suggested that people employed in several other industries have increased risk of lung cancer, including shale oil mining, wood impregnation, roofing and carbon electrode manufacturing [88].

Environmental  factors 

environmental factors Air pollution data show that lung cancer incidence increases by 30–50% in areas with high levels of ambient air pollution compared to areas with lower levels [89,90].

Many studies carried out so far clearly show that the risk of developing lung cancer is much higher in highly urbanized, industrialized regions with a developed transport network, in particular based on the use of internal combustion engines [37].

age The risk of developing lung cancer also increases with age. 

The majority of lung cancers occur after the age of 50

 (96% of cases in men and 95% of cases in women), with about 50% of cases in both sexes occurring in the population over 65 years of age. The risk of developing lung cancer peaks in men in the eighth decade of life and in women at the turn of the sixth and seventh decades of life [25].

Ref

Int J Mol Sci. 2025 Feb 26;26(5):2049. doi: 10.3390/ijms26052049

Lung Cancer—Epidemiology, Pathogenesis, Treatment and

 Molecular Aspect of literature 

 Beata Smolarz 1,*, Honorata Ł

ukasiewicz 2, Dariusz Samulak 3,4, Ewa Piekarska 5, Radosław Kołaciński 5, Hanna Romanowicz 1

Editor: Verena Trett