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E-Cigarettes and Cancer Risk

Boris Mravec, Miroslav Tibensky, Lubica Horvathova and Pavel Babal
DOI: 10.1158/1940-6207.CAPR-19-0346 Published February 2020

Abstract

From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.

Introduction

During the last 50 years, a robust body of evidence has accumulated documenting the negative health consequences of both active tobacco smoking and exposure to secondhand smoke. For example, evaluation of epidemiologic data has shown that at least 12 types of human cancers can be attributed to smoking (1). Therefore, it is not surprising that as information about the negative consequences of smoking is spreading within populations, more and more smokers are choosing e-cigarettes (electronic nicotine-delivery systems) as a “less harmful” source of nicotine.

The first commercially available e-cigarette, a device that is designed to deliver nicotine without tobacco smoke by heating a nicotine solution, was invented in 2003 by the Chinese pharmacist Lik Hon in Hong Kong. Since the introduction of e-cigarettes, they have been become increasingly popular among never-smokers and adolescents, as well as smokers who want to reduce the health risks of smoking or would like to quit smoking (2). This fact is documented by data from the 2011–2018 National Youth Tobacco Survey of U.S. middle and high school students. It was shown that the use of e-cigarettes increased in this group from 1.5% (220,000 students) in 2011 to 20.8% (3.05 million students) in 2018 (3). In the study investigating e-cigarettes use among adults in the United States, it was found that even if the weighted prevalence of current use of e-cigarettes decreased from 2014 to 2016 in some subgroups, the prevalence increased significantly among former smokers from 3.8% in 2014 to 4.8% in 2016 and never-smokers from 0.4% to 0.7% over the same time period (4). This increased popularity of e-cigarettes is also reflected in the variety of e-cigarette device models, numerous brands, and product designs that have been developed over the last few years. Today, the fourth generation of e-cigarettes is available with a heating temperature control mechanism (5, 6). However, even if the levels of carcinogens and toxins are substantially reduced in users of e-cigarettes in comparison with tobacco smokers (7), recent data have shown that the vapor from e-cigarettes also contains, in addition to nicotine, many toxic chemicals found in traditional cigarettes such as acetaldehyde, formaldehyde, acetone, acrolein, chromium, N-nitrosamines, and others (5, 6, 8). Moreover, the vapor derived from e-cigarettes accumulates in the airway epithelium in a similar fashion as smoke from combustible cigarettes (5). These facts indicate that the safety of e-cigarettes remains questionable, and it is still unknown as to whether their use can contribute to cancer development and progression (9). In addition, there are no data about the potential toxic effects of long-term exposure to the vapor produced by nicotine-containing cartridge fluid (10). Therefore, it is not surprising that increased attention is being paid to the effects of substances inhaled by e-cigarette users on their body. However, research into the potentially harmful effects of e-cigarettes in humans is faced with several issues. First, the relatively short period of time during which e-cigarettes have been on the market results in a lack of relevant data, especially those related to the chronic consequences of vapor inhalation (6). Moreover, many factors affecting the composition of inhaled vapor (e.g., device voltage, resistance, temperature, e-liquid flavors and ingredients, nicotine content, and puff topography of e-cigarettes users) and thus the degree of harm have been only recently identified, which makes comparison of previously published studies difficult (5, 6, 11). Nonetheless, there is an increasing number of both cell culture and animal model studies investigating the various biological, toxicological, and immunological effects of exposure to both the liquid used in e-cigarettes and the vapor generated by it on different organ systems, including respiratory, cardiovascular, immune, nervous, or uropoetic (10, 12–15). Importantly, prospective, randomized studies on e-cigarettes are starting to be performed (6).

Recently, the direct modulation of processes in cells or organs by the chemicals present in vapor of e-cigarettes has been studied. These investigations were focused on nicotine because a variety of its harmful effects, including stimulation of cancer growth, are well documented (15–19). In addition, the additives and substances generated by the heating process in e-cigarette cartridges have been widely studied due to their potentially toxic and mutagenic effects (5). However, the potential cancer-related effect of increased activation of the sympathoadrenal system induced by inhalation of nicotine, the primary component of e-cigarettes, has been overlooked in the available studies.

Differences between Combustible and e-Cigarettes

E-cigarettes are considered a less hazardous alternative to combustible cigarettes (20). In support of this, significantly lower levels of toxic substances have been observed in e-cigarette vapor compared with cigarette smoke (21). Consistent with these findings, significantly lower concentrations of biomarkers of exposure to tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons, most volatile organic compounds were observed in e-cigarette users when compared with concentrations found in tobacco smokers (22). However, it should be noted that levels of TSNAs, namely, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, are significantly lower in non-smokers than in e-cigarette smokers (8, 22).

Whereas concentrations of non-nicotine toxic substances in the blood of e-cigarette smokers are significantly lower than in users of combustible cigarettes, the concentration of nicotine is increasing as new generations of e-cigarettes emerge. Even if the first generation of e-cigarettes had inefficient nicotine delivery, users of newer, third-generation models achieve nicotine plasma levels comparable with levels found in smokers of combustible cigarettes (23).

Direct Carcinogenic Effects of e-Cigarettes

In 2014, two studies demonstrated the possible carcinogenic effects of e-cigarettes in immortalized, human bronchial epithelial cells. They found that exposure of these cells in culture medium to the vapor of e-cigarettes induced a similar pattern of gene expression as found in cells exposed to tobacco smoke (24, 25). Later, the findings of Park and colleagues (26) showed that exposure to clinically relevant concentrations of e-cigarette vapor-conditioned media enhanced cancer-associated processes of “at-risk” airways, including a demonstrated capacity for malignant transformation. The authors observed enhanced colony growth in anchorage-independent assays and increased cell invasion–associated morphologic changes in three-dimensional air–liquid interface models. In addition, they found that exposure of mutant epithelial cells to e-cigarette vapor-conditioned media induced airway gene-expression changes similar to those seen with combustible cigarette smoke exposure (26). It was also demonstrated that e-cigarette aerosol increased the proinflammatory cytokines IL6 and IL8 and diminished lung glutathione levels in human and mice lung epithelial cells (27). Importantly, data have shown that increased IL6 levels might, through the STAT3 signaling cascade, promote lung cancer cell growth (28).

In 2017, Canistro and colleagues demonstrated that e-cigarette vapor has powerful comutagenic and cancer-initiating effects in a rat lung cancer model. They showed that e-cigarettes have a booster effect on phase-I carcinogen-bioactivating enzymes, including activators of polycyclic aromatic hydrocarbons (PAH), increased oxygen-free radical production, and DNA oxidation to 8-hydroxy2′-deoxyguanosine (9). Later, Lee and colleagues published data showing an enhanced susceptibility of lung epithelium to oncogenic transformation and tumorigenesis via the action of nicotine metabolites, as well as the subsequent generation of mutagenic nucleotide products in the lung and urinary bladder of mice exposed to e-cigarette vapor, with similar results found in human bronchial epithelial and urothelial cell cultures. In addition, both the DNA-repair activity and expression of the repair proteins XPC and OGG1/2 were significantly reduced in the lungs of mice as well as in human bronchial epithelial cell cultures after exposure to e-cigarette vapor (29, 30). Interestingly, e-cigarettes induce DNA-strand breaks in the human epithelial cell line HaCaT independent of nicotine, while there is evidence that e-cigarette vapor exaggerates the extent of nicotine induced DNA damage (31).

In 2018, Staudt and colleagues demonstrated that even short-term use of e-cigarettes induces tumor- and metastasis-promoting factors related to lung cancer in small airway epithelium (32). It has also been shown that e-cigarettes enhance both the migration and stemness of non–small cell lung cancer cells through expression of the embryonic stem cell factor Sox2 (33, 34). Recently, Tommasi and colleagues reported significant epigenetic changes in the oral cells of users of e-cigarettes. Further analysis revealed that these deregulated genes are associated with signaling pathways implicated in cancer (35).

E-cigarette–related activation of nicotinic receptors in the cancer microenvironment

Nicotinic receptors are expressed on the surface of tumor and immune cells (36, 37), enabling nicotine to directly affect the tumor microenvironment. As a result, this alkaloid has a pronounced tumor-promoting effect on several types of cancers (36, 38).

Through binding to nicotinic receptors, nicotine may potentiate cancer cell survival (39, 40), tumor cell proliferation (41, 42), metastasis, invasion, epithelial–mesenchymal transition (43, 44), and angiogenesis (45, 46). It can also reduce cancer cell apoptosis induced by chemotherapy, radiotherapy, or receptor tyrosine kinase inhibitors (47–49). In addition, nicotine may stimulate proliferation and angiogenesis through the induction of norepinephrine and epinephrine synthesis in colorectal and pancreatic tumor cells, and this effect was blocked by the β-adrenergic receptor antagonists propranolol and ICI-118,551 (46, 50–52).

Indirect “Hidden” Tumor-Promoting Effects of e-Cigarettes

As mentioned above, many studies have been focused on determining the direct effects of e-cigarettes on normal and cancerous cells. However, nicotine inhaled from e-cigarettes may also indirectly exert tumor-promoting effects via stimulation of the sympathoadrenal system (Fig. 1).

Figure 1.
Figure 1.

Schematic depiction of the direct (A and B) and indirect (C) cancer-related effects of compounds inhaled from e-cigarettes.

The sympathoadrenal system stimulates cancer initiation and progression

Over the past two decades, a combination of neuroscientific and oncological research has gradually uncovered the role of the nervous system in cancer. It has been found that the sympathoadrenal system stimulates both carcinogenesis and processes related to tumor progression and metastasis (53–55). Such important effects are induced by norepinephrine released from nerve terminals in tissues innervated by the sympathetic nervous system, as well as by epinephrine and norepinephrine released from the adrenal medulla into the systemic circulation (56). Preclinical and clinical studies have shown that norepinephrine and epinephrine, via binding to β-adrenergic receptors, potentiate the induction of DNA mutations via induction of oxidative stress that reduces the efficiency of DNA-repair mechanisms (57, 58), activate oncogenes (59, 60), induce tumor-promoting inflammation (61), inhibit antitumor immunity by suppression of NK cell activity (62, 63), directly stimulate the proliferation of tumor cells by binding to β-adrenergic receptors expressed by these cells (64–66), protect cancer cells from apoptosis (67, 68), potentiate both neoangiogenesis (69, 70) and lymphatic vessel rearrangement (71) in tumor tissue, enhance matrix metalloproteinase activity (72, 73), and stimulate the mobility (55) and deformability (74) of tumor cells, leading to the development of metastases (75). In addition, published data indicate that catecholamine-induced increase of systemic vascular resistance might redirect blood flow to cancer tissue (76). Moreover, metabolic changes induced by an activated sympathoadrenal nervous system (77) might also affect cancer nourishment. Therefore, it is not surprising that approaches attenuating the effect of norepinephrine and epinephrine (e.g., sympathectomy or administration of β-blockers) can also help to impede the course of cancer progression, as documented by many preclinical and clinical studies (51, 78–86).

Nicotine activates the sympathoadrenal system

Importantly, it is well known that nicotine increases the release of norepinephrine and epinephrine due to its stimulatory effect at several levels of the sympathoadrenal system (87). This effect is mediated by mechanisms including (i) direct stimulation of nerve endings of sympathetic nerves, (ii) activation of nicotinic receptors on cell bodies of sympathetic postganglionic neurons, and (iii) activation of structures of the central nervous system that regulate sympathetic outflow (88). The net stimulatory effect of nicotine on the sympathoadrenal system is documented by the significantly increased plasma norepinephrine and epinephrine levels found in smokers (89). Importantly, the acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine but not the non-nicotine compounds found in the vapor of e-cigarettes (90).

E-Cigarettes and Patients with Cancer

Especially important is the issue of e-cigarettes usage by oncological patients. As noted by Sanford and colleagues, the popularity of e-cigarettes is rising not only in the general population but also among patients with cancer (91). This rise in the use of e-cigarettes in patients with cancer may result from the fact that e-cigarettes are being perceived as a less hazardous alternative to combustible cigarettes (20) due to reports that e-cigarettes produce a smaller quantity of pollutants compared with combustible cigarettes (8). Therefore, patients with cancer may assume that e-cigarettes are almost harmless from the point of view of their disease. However, as mentioned above, the stimulatory effect of nicotine inhaled from e-cigarettes on the sympathoadrenal system may represent an important factor that stimulates progression of their disease. In addition, their use might also be hazardous in individuals with a predisposition for oncological disease. Moreover, as data have shown that epinephrine and norepinephrine act as an angiogenic switch (92) that activates dormant tumors, e-cigarettes might participate in the clinical manifestation of previously dormant cancer. Importantly, the stimulatory effect of nicotine on cancer induction and progression might also be related to other nicotine-delivery systems (e.g., patch, nasal or mouth spray, inhalator, mouth strip, gum, lozenge, and microtabs).

Recommendations for Clinicians

As there are an increasing number of new smokers that start with e-cigarettes instead of combustible cigarettes, these individuals should be informed of the potential interconnection between e-cigarettes and cancer (for recommendations on how to inform patients about the potential harmful effects of e-cigarettes see ref. 93). This information about the stimulatory effects of nicotine and other chemicals inhaled from e-cigarettes on cancer initiation, progression, and development of metastases must be especially provided to oncological patients and individuals with a predisposition to cancer. However, in patients with cancer that are not able to quit smoking and would like to switch from combustible to e-cigarettes, it is necessary to take into consideration the fact that available data indicate that the harmful effects of e-cigarettes are significantly lower than those of combustible cigarettes (7). Therefore, based on available data, e-cigarettes might be recommended to smokers with cancer as a less hazardous alternative (94). In addition, e-cigarettes might also be used in patients with cancer as an effective tool for smoking cessation (95). However, if patients with cancer are informed that even if e-cigarettes are a less hazardous alternative to combustible cigarettes, the risk of potentiating the progression of their disease by e-cigarettes still exists, this might motivate some patients with cancer to quit smoking.

Future Directions

Because e-cigarettes have only been on the market for 16 years (2), it is obvious that our understanding of their effects, especially long term, is still fragmentary. Even if data from recent studies indicate that compounds inhaled from e-cigarettes might participate in carcinogenesis, the indirect effects of nicotine on cancer initiation and progression in smokers of e-cigarettes, mediated by the sympathoadrenal system, have not yet been investigated. Therefore, there is an urgent need for preclinical studies using cancer models in which we can test the effect of long-term inhalation of nicotine from e-cigarettes on the activity of the sympathoadrenal system as determined by plasma epinephrine and norepinephrine levels, as well as their effect on cancer incidence and progression. In these preclinical studies, the fact that e-cigarettes differ in nicotine content (23) needs to be taken in consideration and therefore the effect of different concentrations of this compound on sympathoadrenal system activity and cancer needs to be determined. Similarly, it is necessary to elucidate the effect of e-cigarettes on the incidence and progression of cancer, development of metastases, recurrence of disease, and efficiency of oncological therapy in both retrospective and prospective clinical trials. In studies investigating the effect of e-cigarettes on the progression of disease in patients with cancer, it is necessary to take several factors into consideration:

  • (i) Whether patients with cancer started smoking before or after cancer diagnosis and the duration and frequency of smoking, as the stimulatory effect of nicotine on cancer initiation and progression might be dose and time dependent;

  • (ii) Type of cancer, as some cancers seem to be more sensitive to the stimulatory effect of the sympathoadrenal system (96);

  • (iii) Eventual therapy by β-blockers (e.g., as treatment of hypertension) as these compounds attenuate the effects of epinephrine and norepinephrine released by the sympathoadrenal system on cancer initiation and progression;

  • (iv) The typology of the individual, their age, and extent of social interactions, as these factors affect the activity of the sympathoadrenal system and are known to affect the clinical course of cancer (97).

Conclusion

Although e-cigarettes seem to be less harmful to users and therefore may appear to be a less hazardous alternative to combustible cigarettes, the above-mentioned facts indicating an interconnection between e-cigarettes containing nicotine and cancer support that much effort should be made to strictly regulate the e-cigarette market. This assumption is also supported by the fact that clinical trials investigating the long-term effects of e-cigarettes on cancer incidence and progression are still absent. Therefore, further preclinical and clinical studies focusing on elucidating the potential mechanisms and pathways interconnecting e-cigarettes and cancer are necessary.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by the Slovak Research and Development Agency (APVV-17-0090).

Footnotes

  • Cancer Prev Res 2020;13:137–44

  • Received July 11, 2019.
  • Revision received August 28, 2019.
  • Accepted October 8, 2019.
  • Published first October 16, 2019.

References

  1. 1.↵
    National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. The health consequences of smoking–50 years of progress: a report of the Surgeon General. Atlanta, GA: Centers for Disease Control and Prevention (US); 2014.
  2. 2.↵
    1. Hajek P,
    2. Etter JF,
    3. Benowitz N,
    4. Eissenberg T,
    5. McRobbie H
    . Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit. Addiction 2014;109:1801–10.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Cullen KA,
    2. Ambrose BK,
    3. Gentzke AS,
    4. Apelberg BJ,
    5. Jamal A,
    6. King BA
    . Notes from the field: use of electronic cigarettes and any tobacco product among middle and high school students – United States, 2011–2018. MMWR Morb Mortal Wkly Rep 2018;67:1276–7.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Bao W,
    2. Xu G,
    3. Lu J,
    4. Snetselaar LG,
    5. Wallace RB
    . Changes in electronic cigarette use among adults in the United States, 2014–2016. JAMA 2018;319:2039–41.
    OpenUrlCrossRef
  5. 5.↵
    1. Kaur G,
    2. Pinkston R,
    3. McLemore B,
    4. Dorsey WC,
    5. Batra S
    . Immunological and toxicological risk assessment of e-cigarettes. Eur Respir Rev 2018;27. pii: 170119.
    OpenUrl
  6. 6.↵
    1. Lohler J,
    2. Wollenberg B
    . Are electronic cigarettes a healthier alternative to conventional tobacco smoking? Eur Arch Otorhinolaryngol 2019;276:17–25.
    OpenUrl
  7. 7.↵
    1. Stephens WE
    . Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke. Tob Control 2017 Aug 4 [Epub ahead of print].
  8. 8.↵
    1. Shahab L,
    2. Goniewicz ML,
    3. Blount BC,
    4. Brown J,
    5. McNeill A,
    6. Alwis KU,
    7. et al.
    Nicotine, carcinogen, and toxin exposure in long-term e-cigarette and nicotine replacement therapy users: a cross-sectional study. Ann Intern Med 2017;166:390–400.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Canistro D,
    2. Vivarelli F,
    3. Cirillo S,
    4. Babot Marquillas C,
    5. Buschini A,
    6. Lazzaretti M,
    7. et al.
    E-cigarettes induce toxicological effects that can raise the cancer risk. Sci Rep 2017;7:2028.
    OpenUrl
  10. 10.↵
    1. Hiemstra PS,
    2. Bals R
    . Basic science of electronic cigarettes: assessment in cell culture and in vivo models. Respir Res 2016;17:127.
    OpenUrl
  11. 11.↵
    1. Breland A,
    2. Soule E,
    3. Lopez A,
    4. Ramoa C,
    5. El-Hellani A,
    6. Eissenberg T
    . Electronic cigarettes: what are they and what do they do? Ann N Y Acad Sci 2017;1394:5–30.
    OpenUrlPubMed
  12. 12.↵
    1. Bourke L,
    2. Bauld L,
    3. Bullen C,
    4. Cumberbatch M,
    5. Giovannucci E,
    6. Islami F,
    7. et al.
    E-cigarettes and urologic health: a collaborative review of toxicology, epidemiology, and potential risks. Eur Urol 2017;71:915–23.
    OpenUrl
  13. 13.↵
    1. Benowitz NL,
    2. Burbank AD
    . Cardiovascular toxicity of nicotine: implications for electronic cigarette use. Trends Cardiovasc Med 2016;26:515–23.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Rowell TR,
    2. Reeber SL,
    3. Lee SL,
    4. Harris RA,
    5. Nethery RC,
    6. Herring AH,
    7. et al.
    Flavored e-cigarette liquids reduce proliferation and viability in the CALU3 airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol 2017;313:L52–L66.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Eltorai AE,
    2. Choi AR,
    3. Eltorai AS
    . Impact of electronic cigarettes on various organ systems. Respir Care 2019;64:328–36.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Lien YC,
    2. Wang W,
    3. Kuo LJ,
    4. Liu JJ,
    5. Wei PL,
    6. Ho YS,
    7. et al.
    Nicotine promotes cell migration through alpha7 nicotinic acetylcholine receptor in gastric cancer cells. Ann Surg Oncol 2011;18:2671–9.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Zhang Q,
    2. Tang X,
    3. Zhang ZF,
    4. Velikina R,
    5. Shi S,
    6. Le AD
    . Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways. Clin Cancer Res 2007;13:4686–94.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Shin VY,
    2. Jin HC,
    3. Ng EK,
    4. Yu J,
    5. Leung WK,
    6. Cho CH,
    7. et al.
    Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: involvement of nicotinic acetylcholine receptor (nAChR) and beta-adrenergic receptor signaling pathways. Toxicol Appl Pharmacol 2008;233:254–61.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Calleja-Macias IE,
    2. Kalantari M,
    3. Bernard HU
    . Cholinergic signaling through nicotinic acetylcholine receptors stimulates the proliferation of cervical cancer cells: an explanation for the molecular role of tobacco smoking in cervical carcinogenesis? Int J Cancer 2009;124:1090–6.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Eaton DL,
    2. Kwan LY,
    3. et al.
    National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, et al. Public health consequences of e-cigarettes. Washington, DC: National Academies Press; 2018.
  21. 21.↵
    1. Goniewicz ML,
    2. Knysak J,
    3. Gawron M,
    4. Kosmider L,
    5. Sobczak A,
    6. Kurek J,
    7. et al.
    Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control 2014;23:133–9.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Goniewicz ML,
    2. Smith DM,
    3. Edwards KC,
    4. Blount BC,
    5. Caldwell KL,
    6. Feng J,
    7. et al.
    Comparison of nicotine and toxicant exposure in users of electronic cigarettes and combustible cigarettes. JAMA Netw Open 2018;1:e185937.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Wagener TL,
    2. Floyd EL,
    3. Stepanov I,
    4. Driskill LM,
    5. Frank SG,
    6. Meier E,
    7. et al.
    Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users. Tob Control 2017;26:e23–e8.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Park SJ,
    2. Walser TC,
    3. Perdomo C,
    4. Wang T,
    5. Pagano PC,
    6. Liclican EL,
    7. et al.
    The effect of e-cigarette exposure on airway epithelial cell gene expression and transformation. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6–9; San Diego, CA. Philadelphia (PA): AACR; 2014. Abstract nr B16.
  25. 25.↵
    1. Cressey D
    . E-cigarettes affect cells. Nature 2014;508:159.
    OpenUrl
  26. 26.↵
    1. Park SJ,
    2. Walser TC,
    3. Tran LM,
    4. Perdomo C,
    5. Wang T,
    6. Hong L-S,
    7. et al.
    The biological impact of e-cigarettes on airway epithelial cell transformation and gene expression. J Thorac Oncol 2016;11:35.
    OpenUrl
  27. 27.↵
    1. Lerner CA,
    2. Sundar IK,
    3. Yao H,
    4. Gerloff J,
    5. Ossip DJ,
    6. McIntosh S,
    7. et al.
    Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PLoS One 2015;10:e0116732.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Qu Z,
    2. Sun F,
    3. Zhou J,
    4. Li L,
    5. Shapiro SD,
    6. Xiao G
    . Interleukin-6 prevents the initiation but enhances the progression of lung cancer. Cancer Res 2015;75:3209–15.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Lee HW,
    2. Park SH,
    3. Weng MW,
    4. Wang HT,
    5. Huang WC,
    6. Lepor H,
    7. et al.
    E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci U S A 2018;115:E1560–e9.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Ganapathy V,
    2. Manyanga J,
    3. Brame L,
    4. McGuire D,
    5. Sadhasivam B,
    6. Floyd E,
    7. et al.
    Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. PLoS One 2017;12:e0177780.
    OpenUrl
  31. 31.↵
    1. Yu V,
    2. Rahimy M,
    3. Korrapati A,
    4. Xuan Y,
    5. Zou AE,
    6. Krishnan AR,
    7. et al.
    Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol 2016;52:58–65.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Staudt MR,
    2. Salit J,
    3. Kaner RJ,
    4. Hollmann C,
    5. Crystal RG
    . Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes. Respir Res 2018;19:78.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Schaal CM,
    2. Bora-Singhal N,
    3. Kumar DM,
    4. Chellappan SP
    . Regulation of Sox2 and stemness by nicotine and electronic-cigarettes in non-small cell lung cancer. Mol Cancer 2018;17:149.
    OpenUrl
  34. 34.↵
    1. Zahedi A,
    2. Phandthong R,
    3. Chaili A,
    4. Remark G,
    5. Talbot P
    . Epithelial-to-mesenchymal transition of A549 lung cancer cells exposed to electronic cigarettes. Lung Cancer 2018;122:224–33.
    OpenUrlCrossRef
  35. 35.↵
    1. Tommasi S,
    2. Caliri AW,
    3. Caceres A,
    4. Moreno DE,
    5. Li M,
    6. Chen Y,
    7. et al.
    Deregulation of biologically significant genes and associated molecular pathways in the oral epithelium of electronic cigarette users. Int J Mol Sci 2019;20. pii: E738.
    OpenUrl
  36. 36.↵
    1. Schuller HM
    . Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer 2009;9:195–205.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Fujii T,
    2. Mashimo M,
    3. Moriwaki Y,
    4. Misawa H,
    5. Ono S,
    6. Horiguchi K,
    7. et al.
    Physiological functions of the cholinergic system in immune cells. J Pharmacol Sci 2017;134:1–21.
    OpenUrlCrossRef
  38. 38.↵
    1. Grando SA
    . Connections of nicotine to cancer. Nat Rev Cancer 2014;14:419–29.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Cucina A,
    2. Dinicola S,
    3. Coluccia P,
    4. Proietti S,
    5. D'Anselmi F,
    6. Pasqualato A,
    7. et al.
    Nicotine stimulates proliferation and inhibits apoptosis in colon cancer cell lines through activation of survival pathways. J Surg Res 2012;178:233–41.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Nishioka T,
    2. Guo J,
    3. Yamamoto D,
    4. Chen L,
    5. Huppi P,
    6. Chen CY
    . Nicotine, through upregulating pro-survival signaling, cooperates with NNK to promote transformation. J Cell Biochem 2010;109:152–61.
    OpenUrlPubMed
  41. 41.↵
    1. Shi D,
    2. Guo W,
    3. Chen W,
    4. Fu L,
    5. Wang J,
    6. Tian Y,
    7. et al.
    Nicotine promotes proliferation of human nasopharyngeal carcinoma cells by regulating alpha7AChR, ERK, HIF-1α and VEGF/PEDF signaling. PLoS One 2012;7:e43898.
    OpenUrlPubMed
  42. 42.↵
    1. Dasgupta P,
    2. Rastogi S,
    3. Pillai S,
    4. Ordonez-Ercan D,
    5. Morris M,
    6. Haura E,
    7. et al.
    Nicotine induces cell proliferation by beta-arrestin-mediated activation of Src and Rb-Raf-1 pathways. J Clin Invest 2006;116:2208–17.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Momi N,
    2. Ponnusamy MP,
    3. Kaur S,
    4. Rachagani S,
    5. Kunigal SS,
    6. Chellappan S,
    7. et al.
    Nicotine/cigarette smoke promotes metastasis of pancreatic cancer through alpha7nAChR-mediated MUC4 upregulation. Oncogene 2013;32:1384–95.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Dasgupta P,
    2. Rizwani W,
    3. Pillai S,
    4. Kinkade R,
    5. Kovacs M,
    6. Rastogi S,
    7. et al.
    Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer 2009;124:36–45.
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Natori T,
    2. Sata M,
    3. Washida M,
    4. Hirata Y,
    5. Nagai R,
    6. Makuuchi M
    . Nicotine enhances neovascularization and promotes tumor growth. Mol Cells 2003;16:143–6.
    OpenUrlPubMed
  46. 46.↵
    1. Wong HP,
    2. Yu L,
    3. Lam EK,
    4. Tai EK,
    5. Wu WK,
    6. Cho CH
    . Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation. Toxicol Sci 2007;97:279–87.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Warren GW,
    2. Romano MA,
    3. Kudrimoti MR,
    4. Randall ME,
    5. McGarry RC,
    6. Singh AK,
    7. et al.
    Nicotinic modulation of therapeutic response in vitro and in vivo. Int J Cancer 2012;131:2519–27.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Dinicola S,
    2. Morini V,
    3. Coluccia P,
    4. Proietti S,
    5. D'Anselmi F,
    6. Pasqualato A,
    7. et al.
    Nicotine increases survival in human colon cancer cells treated with chemotherapeutic drugs. Toxicol In Vitro 2013;27:2256–63.
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Imabayashi T,
    2. Uchino J,
    3. Osoreda H,
    4. Tanimura K,
    5. Chihara Y,
    6. Tamiya N,
    7. et al.
    Nicotine induces resistance to erlotinib therapy in non-small-cell lung cancer cells treated with serum from human patients. Cancers 2019;11. pii: E282.
    OpenUrl
  50. 50.↵
    1. Al-Wadei MH,
    2. Al-Wadei HA,
    3. Schuller HM
    . Pancreatic cancer cells and normal pancreatic duct epithelial cells express an autocrine catecholamine loop that is activated by nicotinic acetylcholine receptors α3, α5, and α7. Mol Cancer Res 2012;10:239–49.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    1. Tang J,
    2. Li Z,
    3. Lu L,
    4. Cho CH
    . β-Adrenergic system, a backstage manipulator regulating tumour progression and drug target in cancer therapy. Semin Cancer Biol 2013;23:533–42.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Wong HP,
    2. Yu L,
    3. Lam EK,
    4. Tai EK,
    5. Wu WK,
    6. Cho CH
    . Nicotine promotes cell proliferation via alpha7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells. Toxicol Appl Pharmacol 2007;221:261–7.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. Mravec B,
    2. Gidron Y,
    3. Hulin I
    . Neurobiology of cancer: Interactions between nervous, endocrine and immune systems as a base for monitoring and modulating the tumorigenesis by the brain. Semin Cancer Biol 2008;18:150–63.
    OpenUrlCrossRefPubMed
  54. 54.↵
    1. Kuol N,
    2. Stojanovska L,
    3. Apostolopoulos V,
    4. Nurgali K
    . Crosstalk between cancer and the neuro-immune system. J Neuroimmunol 2018;315:15–23.
    OpenUrl
  55. 55.↵
    1. Cole SW,
    2. Nagaraja AS,
    3. Lutgendorf SK,
    4. Green PA,
    5. Sood AK
    . Sympathetic nervous system regulation of the tumour microenvironment. Nat Rev Cancer 2015;15:563–72.
    OpenUrlCrossRefPubMed
  56. 56.↵
    1. Cole SW,
    2. Sood AK
    . Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer Res 2012;18:1201–6.
    OpenUrlAbstract/FREE Full Text
  57. 57.↵
    1. Flint MS,
    2. Baum A,
    3. Chambers WH,
    4. Jenkins FJ
    . Induction of DNA damage, alteration of DNA repair and transcriptional activation by stress hormones. Psychoneuroendocrinology 2007;32:470–9.
    OpenUrlCrossRefPubMed
  58. 58.↵
    1. Hara MR,
    2. Kovacs JJ,
    3. Whalen EJ,
    4. Rajagopal S,
    5. Strachan RT,
    6. Grant W,
    7. et al.
    A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1. Nature 2011;477:349–53.
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Armaiz-Pena GN,
    2. Allen JK,
    3. Cruz A,
    4. Stone RL,
    5. Nick AM,
    6. Lin YG,
    7. et al.
    Src activation by β-adrenoreceptors is a key switch for tumour metastasis. Nat Commun 2013;4:1403.
    OpenUrlCrossRefPubMed
  60. 60.↵
    1. Shi M,
    2. Liu D,
    3. Duan H,
    4. Qian L,
    5. Wang L,
    6. Niu L,
    7. et al.
    The β2-adrenergic receptor and Her2 comprise a positive feedback loop in human breast cancer cells. Breast Cancer Res Treat 2011;125:351–62.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Huan HB,
    2. Wen XD,
    3. Chen XJ,
    4. Wu L,
    5. Wu LL,
    6. Zhang L,
    7. et al.
    Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells. Brain Behav Immun 2017;59:118–34.
    OpenUrl
  62. 62.↵
    1. Ben-Eliyahu S,
    2. Shakhar G,
    3. Page GG,
    4. Stefanski V,
    5. Shakhar K
    . Suppression of NK cell activity and of resistance to metastasis by stress: a role for adrenal catecholamines and beta-adrenoceptors. Neuroimmunomodulation 2000;8:154–64.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Inbar S,
    2. Neeman E,
    3. Avraham R,
    4. Benish M,
    5. Rosenne E,
    6. Ben-Eliyahu S
    . Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity. PLoS One 2011;6:e19246.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Schuller HM,
    2. Cole B
    . Regulation of cell proliferation by beta-adrenergic receptors in a human lung adenocarcinoma cell line. Carcinogenesis 1989;10:1753–5.
    OpenUrlCrossRefPubMed
  65. 65.↵
    1. Huang XY,
    2. Wang HC,
    3. Yuan Z,
    4. Huang J,
    5. Zheng Q
    . Norepinephrine stimulates pancreatic cancer cell proliferation, migration and invasion via beta-adrenergic receptor-dependent activation of P38/MAPK pathway. Hepatogastroenterology 2012;59:889–93.
    OpenUrlPubMed
  66. 66.↵
    1. Lackovicova L,
    2. Banovska L,
    3. Bundzikova J,
    4. Janega P,
    5. Bizik J,
    6. Kiss A,
    7. et al.
    Chemical sympathectomy suppresses fibrosarcoma development and improves survival of tumor-bearing rats. Neoplasma 2011;58:424–9.
    OpenUrlPubMed
  67. 67.↵
    1. Sastry KS,
    2. Karpova Y,
    3. Prokopovich S,
    4. Smith AJ,
    5. Essau B,
    6. Gersappe A,
    7. et al.
    Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. J Biol Chem 2007;282:14094–100.
    OpenUrlAbstract/FREE Full Text
  68. 68.↵
    1. Horvathova L,
    2. Padova A,
    3. Tillinger A,
    4. Osacka J,
    5. Bizik J,
    6. Mravec B
    . Sympathectomy reduces tumor weight and affects expression of tumor-related genes in melanoma tissue in the mouse. Stress 2016;19:528–34.
    OpenUrl
  69. 69.↵
    1. Yang EV,
    2. Kim SJ,
    3. Donovan EL,
    4. Chen M,
    5. Gross AC,
    6. Webster Marketon JI,
    7. et al.
    Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression. Brain Behav Immun 2009;23:267–75.
    OpenUrlCrossRefPubMed
  70. 70.↵
    1. Park SY,
    2. Kang JH,
    3. Jeong KJ,
    4. Lee J,
    5. Han JW,
    6. Choi WS,
    7. et al.
    Norepinephrine induces VEGF expression and angiogenesis by a hypoxia-inducible factor-1alpha protein-dependent mechanism. Int J Cancer 2011;128:2306–16.
    OpenUrlCrossRefPubMed
  71. 71.↵
    1. Le CP,
    2. Nowell CJ,
    3. Kim-Fuchs C,
    4. Botteri E,
    5. Hiller JG,
    6. Ismail H,
    7. et al.
    Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun 2016;7:10634.
    OpenUrlCrossRefPubMed
  72. 72.↵
    1. Yang EV,
    2. Sood AK,
    3. Chen M,
    4. Li Y,
    5. Eubank TD,
    6. Marsh CB,
    7. et al.
    Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res 2006;66:10357–64.
    OpenUrlAbstract/FREE Full Text
  73. 73.↵
    1. Sood AK,
    2. Bhatty R,
    3. Kamat AA,
    4. Landen CN,
    5. Han L,
    6. Thaker PH,
    7. et al.
    Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res 2006;12:369–75.
    OpenUrlAbstract/FREE Full Text
  74. 74.↵
    1. Kim TH,
    2. Gill NK,
    3. Nyberg KD,
    4. Nguyen AV,
    5. Hohlbauch SV,
    6. Geisse NA,
    7. et al.
    Cancer cells become less deformable and more invasive with activation of beta-adrenergic signaling. J Cell Sci 2016;129:4563–75.
    OpenUrlAbstract/FREE Full Text
  75. 75.↵
    1. Sloan EK,
    2. Priceman SJ,
    3. Cox BF,
    4. Yu S,
    5. Pimentel MA,
    6. Tangkanangnukul V,
    7. et al.
    The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res 2010;70:7042–52.
    OpenUrlAbstract/FREE Full Text
  76. 76.↵
    1. Maccari S,
    2. Buoncervello M,
    3. Rampin A,
    4. Spada M,
    5. Macchia D,
    6. Giordani L,
    7. et al.
    Biphasic effects of propranolol on tumour growth in B16F10 melanoma-bearing mice. Br J Pharmacol 2017;174:139–49.
    OpenUrl
  77. 77.↵
    1. Deibert DC,
    2. DeFronzo RA
    . Epinephrine-induced insulin resistance in man. J Clin Invest 1980;65:717–21.
    OpenUrlCrossRefPubMed
  78. 78.↵
    1. De Giorgi V,
    2. Grazzini M,
    3. Benemei S,
    4. Marchionni N,
    5. Botteri E,
    6. Pennacchioli E,
    7. et al.
    Propranolol for off-label treatment of patients with melanoma: results from a cohort study. JAMA Oncol 2018;4:e172908.
    OpenUrl
  79. 79.↵
    1. Diaz ES,
    2. Karlan BY,
    3. Li AJ
    . Impact of beta blockers on epithelial ovarian cancer survival. Gynecol Oncol 2012;127:375–8.
    OpenUrlCrossRefPubMed
  80. 80.↵
    1. Wang HM,
    2. Liao ZX,
    3. Komaki R,
    4. Welsh JW,
    5. O'Reilly MS,
    6. Chang JY,
    7. et al.
    Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol 2013;24:1312–9.
    OpenUrlCrossRefPubMed
  81. 81.↵
    1. Grytli HH,
    2. Fagerland MW,
    3. Fossa SD,
    4. Tasken KA
    . Association between use of beta-blockers and prostate cancer-specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. Eur Urol 2014;65:635–41.
    OpenUrlCrossRefPubMed
  82. 82.↵
    1. Powe DG,
    2. Voss MJ,
    3. Zanker KS,
    4. Habashy HO,
    5. Green AR,
    6. Ellis IO,
    7. et al.
    Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget 2010;1:628–38.
    OpenUrlCrossRefPubMed
  83. 83.↵
    1. Lemeshow S,
    2. Sorensen HT,
    3. Phillips G,
    4. Yang EV,
    5. Antonsen S,
    6. Riis AH,
    7. et al.
    Beta-blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev 2011;20:2273–9.
    OpenUrlAbstract/FREE Full Text
  84. 84.↵
    1. Baek MH,
    2. Kim DY,
    3. Kim SO,
    4. Kim YJ,
    5. Park YH
    . Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide population-based cohort study. J Gynecol Oncol 2018;29:e82.
    OpenUrl
  85. 85.↵
    1. Spera G,
    2. Fresco R,
    3. Fung H,
    4. Dyck JRB,
    5. Pituskin E,
    6. Paterson I,
    7. et al.
    Beta blockers and improved progression-free survival in patients with advanced HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study. Ann Oncol 2017;28:1836–41.
    OpenUrl
  86. 86.↵
    1. Udumyan R,
    2. Montgomery S,
    3. Fang F,
    4. Almroth H,
    5. Valdimarsdottir U,
    6. Ekbom A,
    7. et al.
    Beta-blocker drug use and survival among patients with pancreatic adenocarcinoma. Cancer Res 2017;77:3700–7.
    OpenUrlAbstract/FREE Full Text
  87. 87.↵
    1. Grassi G,
    2. Seravalle G,
    3. Calhoun DA,
    4. Bolla GB,
    5. Giannattasio C,
    6. Marabini M,
    7. et al.
    Mechanisms responsible for sympathetic activation by cigarette smoking in humans. Circulation 1994;90:248–53.
    OpenUrlAbstract/FREE Full Text
  88. 88.↵
    1. Middlekauff HR,
    2. Park J,
    3. Moheimani RS
    . Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk. J Am Coll Cardiol 2014;64:1740–50.
    OpenUrlFREE Full Text
  89. 89.↵
    1. Cryer PE,
    2. Haymond MW,
    3. Santiago JV,
    4. Shah SD
    . Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N Engl J Med 1976;295:573–7.
    OpenUrlCrossRefPubMed
  90. 90.↵
    1. Moheimani RS,
    2. Bhetraratana M,
    3. Peters KM,
    4. Yang BK,
    5. Yin F,
    6. Gornbein J,
    7. et al.
    Sympathomimetic effects of acute e-cigarette use: role of nicotine and non-nicotine constituents. J Am Heart Assoc 2017;6: pii: e006579.
    OpenUrlAbstract/FREE Full Text
  91. 91.↵
    1. Sanford NN,
    2. Sher DJ,
    3. Xu X,
    4. Aizer AA,
    5. Mahal BA
    . Trends in smoking and e-cigarette use among US patients with cancer, 2014-2017. JAMA Oncol 2019;5:426–8.
    OpenUrl
  92. 92.↵
    1. Zahalka AH,
    2. Arnal-Estape A,
    3. Maryanovich M,
    4. Nakahara F,
    5. Cruz CD,
    6. Finley LWS,
    7. et al.
    Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science 2017;358:321–6.
    OpenUrlAbstract/FREE Full Text
  93. 93.↵
    1. Cummings KM,
    2. Morris PB,
    3. Benowitz NL
    . Another article about e-cigarettes: why should I care? J Am Heart Assoc 2018;7. pii: e009944.
    OpenUrl
  94. 94.↵
    1. Dautzenberg B,
    2. Garelik D
    . Patients with lung cancer: are electronic cigarettes harmful or useful? Lung Cancer 2017;105:42–8.
    OpenUrl
  95. 95.↵
    1. Correa JB,
    2. Brandon KO,
    3. Meltzer LR,
    4. Hoehn HJ,
    5. Pineiro B,
    6. Brandon TH,
    7. et al.
    Electronic cigarette use among patients with cancer: reasons for use, beliefs, and patient-provider communication. Psychooncology 2018;27:1757–64.
    OpenUrl
  96. 96.↵
    1. Rutledge A,
    2. Jobling P,
    3. Walker MM,
    4. Denham JW,
    5. Hondermarck H
    . Spinal cord injuries and nerve dependence in prostate cancer. Trends Cancer 2017;3:812–5.
    OpenUrl
  97. 97.↵
    1. Mirosevic S,
    2. Jo B,
    3. Kraemer HC,
    4. Ershadi M,
    5. Neri E,
    6. Spiegel D
    . "Not just another meta-analysis": sources of heterogeneity in psychosocial treatment effect on cancer survival. Cancer Med 2019;8:363–73.
    OpenUrl
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E-Cigarettes and Cancer Risk
Boris Mravec, Miroslav Tibensky, Lubica Horvathova and Pavel Babal
Cancer Prev Res February 1 2020 (13) (2) 137-144; DOI: 10.1158/1940-6207.CAPR-19-0346
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