Cancer Caused by E-Cigarettes: Comparison
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Please note this is a comparison between Version 2 by Wendy Huang and Version 1 by Bhupendra G Prajapati.

E-Cigarettes work by heating a liquid that usually contains nicotine, flavorings, and other chemicals. When the liquid is heated, users inhale an aerosol into their lungs. While e-cigarettes are generally considered less harmful than traditional tobacco products, they still contain potentially harmful chemicals, which can damage DNA and lead to cancer.

  • cancer
  • e-cigarette
  • head and neck
  • lung
  • bladder
  • breast

1. Introduction

Lik Hong, a Chinese chemist from Hong Kong, created the first commercially successful electronic cigarette (e-cigarette) in 2003. This device heats a nicotine solution to release nicotine without the use of tobacco smoke [1]. When heated, a solution comprising nicotine, moisturizers, and flavorings is typically used in e-cigarettes and vaping devices to supply effluent for inhalation [2]. E-cigarettes are popular among young adults because of reports that they can help smokers stop [3]. This could be so because young adults are drawn to and affected by new trends, especially if they believe that new trends would help them kick their bad habit of smoking cigarettes. Additionally, the fact that they come in a variety of tastes makes them the choice of the majority of users [4]. E-cigarettes are also seen as a superior alternative with fewer health concerns by smokers who are unable to quit [5]. The total prevalence of lifetime e-cigarette vaping was 43.7% across many European nations, with 51.3% of men and 40.5% of women [6]. According to several findings, the prevalence of using e-cigarettes or vaping was, respectively, France (25.46%), Mexico (42.22%), China (24.44%), Australia (12.5%), and the United States (13%) [7,8,9,10,11][7][8][9][10][11].
According to GLOBOCAN 2020, there were 19.3 million new instances of cancer detected in 2020, and there were around 10 million cancer-related deaths. By 2040, GLOBOCAN projects that there will be 28 million new instances of cancer [12]. Breast cancer is more common in women worldwide (11.7%) than lung cancer (11%), followed by colon cancer (10.1%), prostate cancer (7.3%), and stomach cancer (5.6%). Lung cancer, which accounts for 1.8 million (18%) of all cancer-related fatalities, is the most common type, followed by colorectal cancer (9%), liver (8.3%), stomach (7.7%), and breast cancer in women came in second (6.9%). Men are more likely to develop lung, prostate, and colon cancers than women, who are more likely to develop breast, colon, and lung cancers [13,14][13][14]. Additionally, the results of studies showed that using e-cigarettes may also increase the risk of cardiovascular disease and respiratory disease [15,16][15][16].
The long-term health effects of using electronic cigarettes (ECs) are not yet fully understood, as the technology is relatively new, and research is ongoing. However, there is evidence to suggest that EC use may increase the risk of certain types of cancer. The presence of carcinogens in the body fluids of e-cigarette users inherently means that cells are at risk of oncogenic transformation [78,79][17][18]. Nicotine itself may not be a carcinogen, but it is still a highly addictive substance that can have a range of negative health effects, including increased heart rate and blood pressure, constricted blood vessels, and reduced lung function. Nicotine from aerosols or e-cigarette liquids remains on surfaces for weeks or months and reacts with the environment to form nitrates and tobacco-specific nitrosamine compounds, leading to inhalation, ingestion, or dermal contact with carcinogens [80,81][19][20].

2. Head and Neck

Studies using different brands of electronic vapor with or without nicotine, as well as heavy metals like cadmium, lead, nickel, and nitrosamines showed decreased cell viability and apoptosis compared to unexposed controls and significant evidence of necrosis in head and neck squamous cell carcinoma and normal epithelial cell lines. Additionally, exposed cell lines expressed increased H2A histone family member X (-H2AX), a recognizable indicator of double-stranded DNA breakage [82][21]. In a case report, Korrapati A. et al., 2016 [83][22] reported significant DNA double-strand breaks being induced in cells exposed to e-cigarette (0.5–2% volume e-cig vapor over from 24 h to 4 weeks) aerosols as well as an increase in the migration of HN cancer cells after e-cigarette treatment with upregulation of EMT-promoting genes. The case report by Nguyen et al., 2017 [84][23] describes a 59-year-old man who developed a basaloid squamous cell carcinoma after using 30 e-cigarettes every day for the previous 13 years. The authors suggest that e-cigarette use may have contributed to the development of basaloid squamous cell carcinoma, highlighting the potential risks associated with long-term e-cigarette use. The case report by Nguyen et al., 2017 [84][23] describes a 66-year-old man who developed a basaloid squamous cell carcinoma after using e-cigarettes every day for the previous 13 years, 20 times. The authors suggest that e-cigarette use may have contributed to the development of basaloid squamous cell carcinoma, highlighting the potential risks associated with long-term e-cigarette use. The case report by Klawinski et al., 2021 [85][24] describes a 19-year-old man who developed a nonhealing left lateral tongue ulcer later found as a stage IV tumor after using e-cigarettes (0.5 packs) each day for four years. The patient used vaping daily nicotine-delivery systems (Juul) and had no history of tobacco smoking. The authors suggest that e-cigarette use may have contributed to the development of cancer, highlighting the potential risks associated with long-term e-cigarette use.

3. Lungs

Other cancer-causing substances found in e-cigarette aerosols or vapor include formaldehyde, toluene, acetaldehyde, and acrolein as well as heavy metals including cadmium, lead, nickel, nitrosamines, and other substances. The case report by Fracol et al., 2017 [86][25] describes a 51-year-old female who developed breast cancer after using e-cigarettes. Since she believed e-cigarettes were safer than regular cigarettes, she switched to them around three months before her operation and continued to use them at a rate equivalent to her previous 1.5 packs per day. The authors suggest that e-cigarette use may have contributed to the development of breast cancer, highlighting the potential risks associated with long-term e-cigarette use. A case report by Madsen et al., 2016 [87][26] demonstrates that e-cigarette usage (38 mg/mL, 10 mL per week), known as vaping, caused severe liver and lung inflammation in a 45-year-old patient, simulating metastatic disease. Results showed that e-cigarette use promoted Epithelial-mesenchymal transitions (EMT) translocation and interfered with DNA repair mechanisms, which supported the link between e-cigarette use and the progression of cancer. In the case study by Aherrera et al., 2017 [88][27] it was discovered that e-cigarettes contain nicotine and its metabolites as well as a small amount of nickel in the users’ saliva, urine, and exhaled breath. Surprisingly, although the customers do not smoke tobacco, they nevertheless run the danger of developing lung cancer from the nicotine and nickel in e-cigarettes.

4. Bladder

E-cigarette liquids have been found to include aromatic amines, aldehydes, and polyaromatic hydrocarbons, all of which have been found to cause bladder cancer in humans. According to a recent assessment by the National Academy of Sciences, there is currently no evidence connecting e-cigarette usage to the onset or prognosis of cancer, however, e-cigarettes do cause the inhalation of carcinogenic substances. The data indicate that is still growing. A case report by Fuller et al., 2018 [89][28] describes a man aged 39.4 years smoking for 19.9 years. With a wide range of formulas, e-cigarettes have historically been uncontrolled. Benz(a)anthracene and benzo(a)pyrene, aromatic amines, and aldehydes, among other bladder carcinogens, have been found in e-cigarette liquids, vapor, or urine in previous research. The levels of the bladder cancer-causing chemicals 2-naphthylamine and o-toluidine in the urine of e-cigarette users are higher when compared to non-smoking, non-e-cigarette-using controls. Before supplying samples for this investigation, the majority of these subjects had not smoked a typical cigarette in over a year. Although there is evidence to suggest that e-cigarettes are safer than conventional cigarettes, the current study raises the possibility that using an e-cigarette with varying liquid and vapor control formulas may not be completely risk-free from the perspective of bladder cancer. The case report by Viswam et al., 2018 [90][29] describes a 16-year-old girl who developed hypersensitivity pneumonitis after using e-cigarettes for several months. The patient presented with symptoms such as cough, shortness of breath, and fever, and was diagnosed with hypersensitivity pneumonitis based on clinical and radiographic findings. The authors suggest that e-cigarette use may have contributed to the development of hypersensitivity pneumonitis in this patient, highlighting the potential risks associated with e-cigarettes on lung health. To fully comprehend the effects of e-cigarettes, use on lung health, more research is required. One of the first studies by Lee et al., 2018 [91][30] showed that the nitrosamines and downstream metabolites of nicotine present in ECs put E-cigarette users at greater risk than non-users for developing lung or bladder malignancies or heart disease. The case report by Bjurlin et al., 2021 [92][31] shows in contrast to non-e-cigarette users, those who use e-cigarettes have higher levels of carcinogens that can be metabolized into several compounds that can cause bladder cancer, which can be identified by urine sampling.

5. Breast

Breast cancer (BC) is the cancer that affects women most frequently in the United States, accounting for almost one-third of all cancer diagnoses in this population and more than 18–20% of all cancer-related deaths in women. There is evidence that e-cigarettes promote lung metastasis of human breast cancer cells. This is an important contribution to understanding the potential risks that e-cigarettes pose to human health and requires further research [93][32]. Previous research has shown that e-cigarette use increases lung carcinogenesis by causing the production of DNA adducts in the lungs. Additionally, a case report by Ryu et al., 2018 [94][33] demonstrates that inhaling e-cigarettes may cause the release of oncogenic cytokines or microRNA from both pulmonary cells and breast cancer cells, promoting lung colonization of breast cancer cells like the colonization of conventional CS cells, which promotes the metastasis of breast cancer-causing breast cells. A study by Kien Pham et al., 2020 [95][34] in the context of e-cigarette-enhanced BC development and metastasis, evaluates the crucial involvement of myeloid cells and related signaling pathways. The microenvironment of every organ in the body is typically tumor-suppressive under physiological circumstances. However, a tumor-promoting microenvironment can develop as a result of persistent inflammation brought on by a variety of causes. In a study by Hyunh et al., 2020 [96][35] e-cigarette inhalation, similar to conventional cigarettes, may induce the release of oncogenic cytokines or microRNAs from both lung and breast cancer cells, thereby promoting lung colonization by breast cancer cells. A third possibility is that exposure to e-cigarettes may improve the survival of breast cancer cells during the invasion and nesting process. Evidence from the literature suggests that cancer cells are prone to apoptosis during metastasis.

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