Risk Factors of Glioblastoma Multiforme: Comparison
Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Irena Baranowska-Bosiacka.
Glioblastoma multiforme (GBM) is one of the most aggressive malignancies and also the most common malignant primary tumor of the brain and central nervous system, accounting for 14.5% of all central nervous system tumors and 48.6% of malignant central nervous system tumors. The median overall survival (OS) of GBM patients is low, at only 15 months.
  • glioblastoma multiforme
  • risk factor
  • Smoking
  • head injury
  • alcohol use
  • electromagnetic radiation

1. Tobacco Smoking and Nitrosamines

Cigarette smoking has not been clearly linked to an increased risk of developing Glioblastoma multiforme (GBM)[152,153][1][2] and glioma [152,153,154][1][2][3]. Because of the mixed findings, further attempts to establish a correlation or lack thereof are desirable, especially because cigarette smoke is a proven risk factor for the development of malignancies in certain organs. Cigarette smoke mutagens, such as tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs), penetrate the blood–brain barrier [155][4], which may potentially affect the development of central nervous system tumors [156][5]. Considerable scientific evidence also points to the carcinogenic effect of TSNA in causing malignancies of the lung, pancreas, esophagus, and oral cavity. The most recent International Agency for Research on Cancer (IARC) monograph did not classify the nervous system as an organ in which carcinogenesis is caused by tobacco products [156][5].
Nitrosamines can originate from cigarette smoke, but also from the reaction of nitrates and nitrites used in meat products—hams, bacon, and sausages. N-nitrosodimethylamine (NDMA) is one of the most common nitrosamines in food [157,158,159][6][7][8]. NDMA is a potent carcinogen capable of inducing cancer in animal models [160][9]. Nitrates present in food entering the digestive system are absorbed into the blood and then secreted into the saliva. Following ingestion, they are passed into the stomach, where they are converted to nitrosamines in an acidic environment [161][10]. A study of patients diagnosed between 1987 and 1991 in Israel found that N-nitroso compounds were not directly linked to brain tumors [162][11].
In a study by Michaud et al. [163][12], neither the group consuming the most processed meat products nor the nitrate-exposed group had an increased risk of glioma (RR: 0.92; 95% CI: 0.48, 1.77 and RR: 1.02; 95% CI: 0.66, 1.58, respectively).
A meta-analysis by Saneei et al. [164][13] included data from 18 observational studies and found no association between the consumption of processed red meat and increased incidence of glioma.

2. Race/Ethnicity

There is a limited association between specific ethnic groups and the risk of developing GBM. Ostrom et al. [100][14] reported a 2.97 times higher incidence of GBM in Caucasians compared to Asians, and a 1.99 times higher incidence in Caucasians compared to African Americans.
A 2006 study by Fukushima et al. [165][15] compared mutations found in primary GBM in a Japanese group with mutations found in the Swiss group described by Ohgaki et al. [99][16]. The results of the study by Fukushima et al. [165][15] suggest high molecular similarity of GBM, despite the different genetic backgrounds of Asians and Caucasians.

3. Ionizing Radiation

Ionizing radiation is a recognized risk factor for many cancers. Direct damage to genetic material or the generation of free radicals in the vicinity of DNA strands results in an increased incidence of mutations within the genetic material of cells. Since controlled clinical trials on the effects of radiation on carcinogenesis are not feasible for ethical reasons, case–control studies play a major role in describing this phenomenon. Ron et al. [167][17] already in 1988 linked doses of 1–2 Gy to an increased risk of neuronal tumors. A literature review by Bowers et al. [168][18] in 2013 documented an 8.1–52.3 times increased risk of central nervous system cancer after radiotherapy to the head for a CNS tumor in childhood compared to the general population, proportional to dose.
Most studies on the relationship between computed tomography (CT) and the risk of glioma development in children have not shown an increased risk, apart from a study describing one excess brain tumor per 10,000 patients over a 10-year period after exposure to one CT scan [169][19].

4. Head Injury

Because of the described anecdotal cases of CNS tumors (not just GBM) being diagnosed after head trauma, further studies on head trauma as an etiologic factor of brain tumors have been conducted, with mixed results. Unfortunately, the available research is quite limited. Proving a causal relationship is very difficult in this case [170][20]. In a study on the Danish population, gliomas were not diagnosed more frequently in patients after head injury—the standardized incidence ratio (SIR) after the first year was 1.0 for glioma (CI = 0.8–1.2) compared to the general Danish population. Tumors detected during the first-year period were not considered due to the detection of incidental lesions already existing during the trauma [171][21]. A study conducted in 1980 showed an increased odds ratio (odds ratio = 2.0, p = 0.01) in women compared with the control group in the incidence of meningiomas following head trauma [172][22]. In contrast, a case–control study evaluating the incidence of meningiomas and gliomas after head injury documented a higher risk of meningiomas, but a lower risk of gliomas (OR = 1.2, 95% CI: 0.9–1.5 for any injury; OR = 1.1, 95% CI: 0.7–1.6) [173][23]. Potential problems with the study may include the use of diagnostic methods using ionizing radiation, which is a proven risk factor for cancer, and potential problems with recalling past injuries and the non-standardized assessment of their extent.

5. Obesity

Adipose tissue has many functions in the human body. In addition to storing nutrients in the form of fats, it has a secretory role, for example, secreting estrogens [174][24] and pro-inflammatory substances [175,176][25][26]. For these reasons, it may have a potential impact on the development of cancer, including GBM.
Current data suggest that lLow body weight (BMI < 18.5 kg/m2) at age 21 is associated with a lower risk of developing gliomas later in life, although the results were only statistically significant in the group of women [177][27]. Moore et al. [178][28] found that patients who were obese at age 18 (BMI 30.0–34.9 kg/m2) had nearly four times the risk of developing gliomas compared to those who had a BMI of 18.5–24.9 kg/m2 at age 18 (RR = 3.74; 95% CI = 2.03–6.90; p trend = 0.003).
In the study by Kaplan et al. [162][11], increased fat and cholesterol consumption was inversely related to the incidence of glioma (high fat intake OR = 0.45, 95% Cl 0.20–1.07; high cholesterol intake: OR = 0.38, 95% Cl 0.14–1.01). Cote et al. [174][24] observed an inverse relationship between hyperlipidemia and glioma.
A study on a group of patients diagnosed between 1987 and 1991 in Israel found a relationship between the occurrence of gliomas and meningiomas and a protein-rich diet (OR = 1.94, 95% CI 1.03–3.63) [162][11]. Wiedmann et al. [119][29] did not observe an increased risk of glioma in overweight or obese individuals.
Seliger et al. [179][30] described a decrease in the risk of GBM in people with diabetes (OR = 0.69; 95% CI = 0.51–0.94). The decrease in risk was most pronounced in men with more than 5 years of disease or with poor glycemic control (HbA1c ≥ 8). In contrast, the effect of lower GBM risk was absent in women (OR = 0.85; 95% CI = 0.53–1.36).

6. Growth

Although a tall stature is associated with a higher incidence of certain cancers [180[31][32],181], the exact mechanism of this phenomenon has not been explained. It is likely that the insulin-like growth factor (IGF) and growth hormone (GH) pathways, which determine growth and final height in humans, are involved. The IGF concentrations peak at puberty and then decline in the third decade of life [182][33]. More than 80% of GBM tumors overexpress insulin-like growth factor binding protein-2 (IGFBP-2), one of the biomarkers of GBM malignancy [183,184][34][35]. In less aggressive tumors, IGFBP-2 is usually undetectable and appears with tumor progression [185][36].
In the paper published by Moore et al. [178][28], the risk of developing glioma among tall people (over 190 cm) was twice as high as that among people less than 160 cm tall (multivariate relative risk [RR] = 2.12; 95% confidence interval [CI] = 1.18–3.81; p trend = 0.006). In contrast, a study by Little et al. [176][26] did not link adult height to the risk of developing glioma.

7. Metals

The International Agency for Research on Cancer (IARC) lists cadmium, cadmium compounds, chromium compounds, and nickel compounds as human carcinogens, with lead as a potential carcinogen. None of these have been found to be associated with brain tumors. The ability of some heavy metals to penetrate the blood–brain barrier and to enter through the olfactory nerve pathway [186][37] prompts a closer examination of their effects on the risk of GBM.
A study conducted in 1970 examining job-exposure matrix (JEM)-based exposures to individual metals did not observe an increased risk of glioma in relation to occupational exposure to chromium, nickel, or lead among 2.8 million male workers (n = 3363 cases of glioma).
Parent et al. [187][38] reported an increased incidence of glioma associated with occupational exposure to arsenic, mercury, and petroleum products. However, they did not report an increased OR for glioma for welders exposed to lead, cadmium, or welding fumes [187][38]. Lead may also induce oxidative stress and disturbances in energy metabolism, induce apoptosis, and affect certain signaling pathways [187,188,189,190,191][38][39][40][41][42]. A meta-analysis by Ahn et al. [192][43] reported an increased risk of malignant brain tumors associated with lead exposure (pooled OR = 1.13, 95% CI: 1.04–1.24). Rajaraman et al. [193][44] observed no relationship between lead exposure and glioma risk.
Bhatti et al. [191][42] examined the potential carcinogenicity of lead by analyzing the modification of single-nucleotide polymorphisms (SNPs) within genes functionally related to oxidative stress. The study included 494 controls, 176 GBM patients, and 134 meningioma patients who were evaluated for occupational lead exposure. Rac family small GTPase 2 (RAC2) and glutathione peroxidase 1 (GPX1) gene polymorphisms significantly modified the relationship between cumulative lead exposure and GBM risk.

8. Nutritional Factors, Chemicals, and Pesticides

Brain tissue necrosis associated with GBM invasion leads to the release of triglycerides and may be accompanied by the release of toxins co-stored in phospholipid-rich neural tissue [194][45].
In a 1992 study using data from the Canadian National Cancer Incidence Database and Provincial Cancer Registries, Morrison et al. [195][46] found a statistically significant relationship between the risk of death from GBM and increased exposure to fuel/oil emissions (test for trend p = 0.03, RR for highest-exposure quartile was 2.11, 95% confidence interval = 0.89–5.01). They further suggested inverse associations of cholesterol and fat consumption with brain tumor risk, which they described as inconsistent with other studies [162][11].
In a study on T98G and U138-MG GBM cells, researchers attempted to determine the cytotoxic or proliferative effects of chemical compounds. The proliferative effect occurred only for the T98G line with perfluorodecanoic acid (PFDA), perfluoroacetate sulfonate (PFOS), and testosterone. However, perfluorinated salt (ammonium perfluoroacetate) and dehydroepiandrosterone (DHEA) showed no proliferation-stimulating effect, suggesting that the proliferative effect is not mediated by androgen receptor activation. The authors concluded that exposure to certain substances released during necrolysis may affect the subsequent growth of GBM and the adoption of more aggressive forms of GBM [194].
An in vitro study subjected the U87 GBM cell line to long-term exposure to low doses of a mixture of pesticides (chlorpyrifos-ethyl, deltamethrin, metiram, and glyphosate). Exposure resulted in the development of resistance to chemotherapeutics (cisplatin, telosomide, 5-fluorouracil, among others) and increased expression of ATP-binding cassette (ABC) proteins [196][47].
Kuan et al. [197][48] reported weak or null associations between food groups, nutrients, or dietary patterns and glioma risk. They found no trends of decreasing glioma risk with increasing intake of total fruit, citrus fruit, and fiber, and a healthy diet.

9. Coffee and Tea

Coffee and tea may have potential cancer-protective effects. The presence of antioxidants, such as polyphenols, caffeic acid, diterpenes (including kahweol and cafestol), and heterocyclic compounds [198,199[49][50][51][52],200,201], could explain the molecular basis for this finding. A study by Kang et al. [201][52] reported the inhibition of GBM cell growth in vitro after exposure to caffeine by the inhibition of inositol trisphosphate receptor subtype 3. Polyphenol (2)-epigallocatechin-3-gallate restores the expression of methylated (silenced) genes in cancer cells, including MGMT, a protein with a DNA repair function [202][53]. Huber et al. [203][54] described elevated MGMT protein levels in rat livers after exposure to Kahweol and Cafestol (diterpenes).
Studies on the effects of coffee and tea on glioma risk are inconclusive. Holick et al. [204][55] reported an inverse relationship between caffeine consumption and glioma risk among men, but not among women. In contrast, in a cohort of 545,771 participants, Dubrow et al. [205][56] found no reduction in glioma risk with increased coffee and tea consumption. However, in a full multivariate model, there was an almost statistically significant inverse relationship between the highest level of tea consumption (three cups per day) and glioma risk (HR = 0.75; 95% CI, 0.57–1.00).
In a more recent study on a British population cohort (2,201,249 person-years and 364 GBM cases), Creed et al. [206][57] observed an inverse relationship between tea consumption and glioma risk that was statistically significant for all gliomas, and for GBM in men. In the same year, Cote et al. [207][58] published a paper using data from the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow-Up Study (HPFS) (6,022,741 person-years; 362 cases of GBM). The authors did not observe a relationship between coffee consumption and glioma risk, but noted a borderline inverse relationship between tea consumption and glioma risk for the combined cohort of men and women (HR for >2 cups/day versus <1 cup/week 0.73, 95% CI: 0.49–1.10, p-trend = 0.05).
Michaud et al. [208][59] observed a statistically significant inverse relationship between coffee intake and glioma risk in a group consuming 100 mL or more of coffee or tea per day compared to a group consuming less than 100 mL of coffee or tea per day. Based on the six studies included in the meta-analysis, Malerba et al. [209][60] suggested no association between coffee or tea consumption and the risk of glioma, but their work had limitations due to the small number of papers analyzed.

10. Alcohol Use

Alcohol can cross the blood–brain barrier and, therefore, can affect glial cells; in addition, it is a recognized risk factor in multiple cancers [210][61]. The metabolism of alcohol (at higher concentrations in the body) produces acetaldehyde and reactive oxygen species that have toxic effects on cells; acetaldehyde has been shown to be neurocarcinogenic in animals [211][62]. Additionally, alcoholic beverages contain N-nitroso compounds that cause brain tumors in animals [211,212,213][62][63][64]. Despite this, the study by Qi et al. [214][65] based on 19 meta-analyses reported no association between glioma incidence and alcohol consumption. These observations were confirmed by a recent study by Cote et al. [215][66], who even indicated that low to moderate alcohol consumption may reduce the risk of glioma.

11. Sleep and Melatonin

Samatic et al. [216][67] noticed that sleep duration is not linked with the risk of glioma. Oreskovic et al. [217][68] reported that there are mechanisms of pro-tumor effects of sleep disorders, including phase shifts, decreased antioxidant levels, immunosuppression, metabolic changes, melatonin deficiency, cognitive impairment, or epigenetic changes. All of these changes significantly affect the poorer prognosis of patients with malignant brain tumors and are potential exacerbating factors for tumor progression. In addition, the occurrence of a brain tumor contributes to sleep disorders.
Lissoni et al. [218][69] evaluated the effects of melatonin co-treatment in patients with GBM undergoing radical or adjuvant radiotherapy. They observed that the patient survival percentage of the RT and melatonin group was significantly higher than that of the RT alone group (6/14 vs. 1/16 patients).
Cutando et al. [219][70] reported that melatonin administration reduces the incidence of malignant tumors in vivo and increases the survival time of patients with GBM treated by radiotherapy. A study by Martin et al. [220][71] showed that melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death. Furthermore, the melatonin/TRAIL combination significantly increases apoptotic cell death compared to TRAIL alone. A study by Zheng et al. [221][72] confirmed the anti-glioma function of melatonin to be mediated partly by suppressing glioma stem cell (GSC) properties through EZH2-NOTCH-1 signaling.

12. Inflammation

Even in a healthy body, gene mutations can lead to tumorigenesis and GBM. Numerous mechanisms are in place to offset these processes so that altered cells are effectively destroyed by the immune system before tumor formation [222,223][73][74]. Even when a tumor forms, the immune system can destroy it at an early stage. A molecular mechanism that facilitates this process is inflammation [224][75]. Chronic inflammation, on the other hand, can facilitate tumor formation [225][76] by damaging DNA, resulting in mutations and tumorigenesis [225,226][76][77]. Additionally, chronic inflammation triggers mechanisms that can inhibit an otherwise robust immune system response [227][78] and thus inhibit the immune system from fighting newly formed cancer cells. For this reason, the factors that trigger this physiological state will increase susceptibility to cancer. Some of the best-studied inflammation-related factors involved in GMB are tumor necrosis factor α (TNFα) and interleukins 1 and 6 (IL-1 and IL-6).
Tumor necrosis factor α (TNFα) is a soluble cytokine involved in directing the systemic inflammatory response [228][79]. It can exert antitumor effects on glioma cells, but can also enhance tumor progression. TNFα can facilitate angiogenesis by increasing epidermal growth factor receptor (EGFR) activity [229][80]; it induces immune cell suppression through the activation of the NF-κB and STAT3 pathways [230][81], and decreases the expression of the tumor-suppressor gene PTEN in glioma [231][82]. Our results suggest that TNFα is involved in reduced macrophage infiltration, suggesting that TNFα plays a suppressive role by demonstrating the ability to promote tumorigenesis [232][83]. Since abnormal epidermal growth factor receptor EGFR signaling is widespread in GBM, EGFR inhibition seemed to be a promising therapeutic strategy. However, EGFR inhibition in GBM causes a rapid upregulation of TNFα, which in turn leads to the activation of the JNK-Axl-ERK signaling pathway involved in resistance to EGFR inhibition [233][84]. A previous study showed that TNFα induces the upregulation of angiogenic factors in malignant glioma cells, which plays a role in RNA stabilization [234][85]. This confirms that TNFα in GBM cells may play an important role in tumor progression.
Interleukin 1 (IL-1) is a potent inducer of proangiogenesis and proinvasion factors, such as VEGF, in human astrocytes and glioma cells. IGF2 induction [235,236][86][87] is strongly stimulated by IL-1 in astrocytes [237][88]. IL-1 is also a major inducer of astrocyte/glioma miR-155, a microRNA involved in inflammation-induced cancer formation [238][89]. The specific microRNA (miR-155) targets cytokine signaling suppressors, potentially leading to the overactivation of STAT3, a transcription factor important in glioma progression.
IL-1α has been implicated in cancer pathogenesis, but there is little evidence of its role in GBM. To date, its function has been shown to be both pro- and anti-tumor in various cancer types [239][90]. IL-1α secretion by tumor cells causes the constitutive activation of NF-κB, which results in the expression of genes involved in the cascade of metastatic processes and angiogenesis [240][91].
GBMs have been shown to produce large amounts of IL-1β, which plays a key role in glioma aggressiveness and survival. IL-1β is a major pro-inflammatory cytokine that triggers a number of tumorigenic processes by activating various cells to upregulate key molecules involved in oncogenic events. Elevated levels of IL-1β have been observed in cultures of GBM cell lines [241][92] and in samples from human GBM tumors [242][93]. IL-1β receptor (IL-1R) is found in GBM cells and tissues [243][94]. The binding of IL-1β to IL-1R activates a cascade of NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways [244][95]. IL-1β-induced ERK activation can also have mitogenic effects on human glioma U373MG cells and significantly increase GBM cell proliferation [245][96]. IL-1β-dependent activation of the NF-κB, p38 MAPK, and JNK pathways in GBM cells also leads to increased expression of VEGF, which promotes angiogenesis, migration, and invasion [246][97]. In addition, IL-1β-mediated up-regulation of factor HIF-1 [247][98] is involved in molecular responses to hypoxia, which is a key component of GBM progression.
The glioma environment is subject to chronic inflammation, and IL-6 is one of the cytokines strongly associated with the chronic inflammatory phenotype often associated with GBM. Tumor-associated macrophages make up a large majority of noncancerous cells in tumors and are major producers of IL-6 [248][99]. Interleukin 6 (IL-6) has been shown to be a factor involved in the malignant progression of glioma [249][100]—it promotes regeneration, invasion, and angiogenesis. In glioma, the elevated expression of IL-6 and its receptor is associated with poor patient survival [250][101]. IL-6 promotes tumor survival by suppressing immune surveillance through the recruitment and stimulation of tumor-associated myeloid-derived suppressor cells and neutrophils. This paralyzes the response of surrounding type-1 helper T cells and cytolytic T cells, ultimately leading to T cell dysfunction and the inhibition of tumor cell clearance. IL-6 is specifically involved in GBM as the stimulation of brain tumor cells by IL-6 promotes three major signal transduction pathways involved in gliogenesis—(1) p42/p44-MAPK, dysregulated in approximately one-third of all cancers and strongly involved in the detection and processing of stress signals [251][102]; (2) PI3K/AKT, a signaling pathway associated with enhancing angiogenesis, activating the EMT transition to increase invasion, and promoting metastasis [252][103]; and (3) JAK-STAT3, a pathway that blocks tumor recognition by immune cells and promotes cell cycle progression and the inhibition of apoptosis [253][104].

13. Electromagnetic Radiation

With the popularization of electronic devices, such as microwave ovens and cell phones, the impact of exposure to electromagnetic waves and the risk of developing CNS tumors became a controversial topic. The impact of phones on tumor development remains inconclusive due to the mixed results from studies, the relatively short time since the prevalence of smartphones, and the numerous confounding factors in the research.
Today, people are commonly exposed to radio-frequency electromagnetic fields (RF-EMF) (30 kHz–30 GHz) through electronic devices, such as cell phones, cordless phones, radios, and Bluetooth. These devices are located in close proximity to users so that even low-power transmitters are not precluded from potential effects on health. The specific RF energy absorption rate (SAR) of the most common source, mobile telephones, is influenced by many factors, such as the design of the device, the position of the antenna in relation to the user’s head, the anatomy of the user’s head, how the phone is held, and the quality of the connection between the cell phone and the network station. A working group [254][105] in 2011 concluded that, despite the high risk of error in the available studies, the potential carcinogenic effects of RF-EMF cannot be ruled out.
A pooled analysis of Swedish case–control studies of people who had used cell phones for more than 25 years was conducted by Hardell and Carlberg [255][106], showing that the OR of developing glioma was 3.0 (95% CI: 1.7–5.2). In contrast, Villeneuve et al. [256][107] suggested that the lack of increase in glioma incidence rates with the increasing popularization of cell phones supports the lack of a causal relationship.
In a study published in 2010 [257][108], a group who used a cell phone at least once a week over a six-month period had a lower risk of developing glioma than the group who never used a cell phone (OR = 0.81 (95% CI: 0.70–0.94)), but the most exposed (10th decile (≥1640 h)) in terms of cumulative exposure had a 40% higher risk of developing glioma (OR = 1.40, 95% CI = 1.03–1.89). This indicates the possible presence of confounding factors, study biases, and suboptimal selection of study participants.
In studies on the effect of cellphone use on the survival of GBM patients, Olsson et al. [258][109] did not report any reduced OS compared to those who did not use cell phones regularly.

References

  1. Blowers, L.; Preston-Martin, S.; Mack, W.J. Dietary and other lifestyle factors of women with brain gliomas in Los Angeles County (California, USA). Cancer Causes Control 1997, 8, 5–12.
  2. Zheng, T.; Cantor, K.P.; Zhang, Y.; Chiu, B.C.H.; Lynch, C.F. Risk of brain glioma not associated with cigarette smoking or use of other tobacco products in Iowa. Cancer Epidemiol. Biomark. Prev. 2001, 10, 413–414.
  3. Lachance, D.H.; Yang, P.; Johnson, D.R.; Decker, P.A.; Kollmeyer, T.M.; McCoy, L.S.; Rice, T.; Xiao, Y.; Ali-Osman, F.; Wang, F.; et al. Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking. Am. J. Epidemiol. 2011, 174, 574–581.
  4. Das, L.; Patel, B.; Patri, M. Adolescence benzopyrene treatment induces learning and memory impairment and anxiolytic like behavioral response altering neuronal morphology of hippocampus in adult male Wistar rats. Toxicol. Rep. 2019, 6, 1104–1113.
  5. Zhang, L.; Sharma, S.; Zhu, L.X.; Kogai, T.; Hershman, J.M.; Brent, G.A.; Dubinett, S.M.; Huang, M. Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells. Cancer Res. 2003, 63, 5065–5072.
  6. Humans, IWGotEoCRt, and IARC Working Group. Tobacco smoke and involuntary smoking. IARC Monogr. Eval. Carcinog. Risks Hum. 2004, 83, 1–1438.
  7. Jakszyn, P.; Agudo, A.; Berenguer, A.; Ibáñez, R.; Amiano, P.; Pera, G.; Ardanaz, E.; Barricarte, A.; Chirlaque, M.D.; Dorronsoro, M.; et al. Intake and food sources of nitrites and N-nitrosodimethylamine in Spain. Public Health Nutr. 2006, 9, 785–791.
  8. Tricker, A.R.; Pfundstein, B.; Theobald, E.; Preussmann, R.; Spiegelhalder, B. Mean daily intake of volatile N-nitrosamines from foods and beverages in West Germany in 1989–1990. Food Chem. Toxicol. 1991, 29, 729–732.
  9. Anderson, L.M.; Souliotis, V.L.; Chhabra, S.K.; Moskal, T.J.; Harbaugh, S.D.; Kyrtopoulos, S.A. N-nitrosodimethylamine-derived O(6)-methylguanine in DNA of monkey gastrointestinal and urogenital organs and enhancement by ethanol. Int. J. Cancer 1996, 66, 130–134.
  10. Honikel, K.O. The use and control of nitrate and nitrite for the processing of meat products. Meat Sci. 2008, 78, 68–76.
  11. Kaplan, S.; Novikov, I.; Modan, B. Nutritional factors in the etiology of brain tumors: Potential role of nitrosamines, fat, and cholesterol. Am. J. Epidemiol. 1997, 146, 832–841.
  12. Michaud, D.S.; Holick, C.N.; Batchelor, T.T.; Giovannucci, E.; Hunter, D.J. Prospective study of meat intake and dietary nitrates, nitrites, and nitrosamines and risk of adult glioma. Am. J. Clin. Nutr. 2009, 90, 570–577.
  13. Saneei, P.; Willett, W.; Esmaillzadeh, A. Red and processed meat consumption and risk of glioma in adults: A systematic review and meta-analysis of observational studies. J. Res. Med. Sci. 2015, 20, 602–612.
  14. Ostrom, Q.T.; Gittleman, H.; Farah, P.; Ondracek, A.; Chen, Y.; Wolinsky, Y.; Stroup, N.E.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro-Oncology 2013, 15, ii1–ii56.
  15. Fukushima, T.; Favereaux, A.; Huang, H.; Shimizu, T.; Yonekawa, Y.; Nakazato, Y.; Ohagki, H. Genetic alterations in primary glioblastomas in Japan. J. Neuropathol. Exp. Neurol. 2006, 65, 12–18.
  16. Ohgaki, H.; Dessen, P.; Jourde, B.; Horstmann, S.; Nishikawa, T.; Di Patre, P.L.; Burkhard, C.; Schüler, D.; Probst-Hensch, N.M.; Maiorka, P.C.; et al. Genetic pathways to glioblastoma: A population-based study. Cancer Res. 2004, 64, 6892–6899.
  17. Ron, E.; Modan, B.; Boice, J.D.; Alfandary, E.; Stovall, M.; Chetrit, A.; Katz, L. Tumors of the Brain and Nervous System after Radiotherapy in Childhood. N. Engl. J. Med. 1988, 319, 1033–1039.
  18. Bowers, D.C.; Nathan, P.C.; Constine, L.; Woodman, C.; Bhatia, S.; Keller, K.; Bashore, L. Subsequent neoplasms of the CNS among survivors of childhood cancer: A systematic review. Lancet Oncol. 2013, 14, e321–e328.
  19. Pearce, M.S.; Salotti, J.A.; Little, M.P.; McHugh, K.; Lee, C.; Kim, K.P.; Howe, N.L.; Ronckers, C.M.; Rajaraman, P.; Craft, A.W.; et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: A retrospective cohort study. Lancet 2012, 380, 499–505.
  20. Simińska, D.; Kojder, K.; Jeżewski, D.; Kojder, I.; Skórka, M.; Gutowska, I.; Chlubek, D.; Baranowska-Bosiacka, I. The Pathophysiology of Post-Traumatic Glioma. Int. J. Mol. Sci. 2018, 19, 2445.
  21. Inskip, P.D.; Mellemkjaer, L.; Gridley, G.; Olsen, J.H. Incidence of intracranial tumors following hospitalization for head injuries (Denmark). Cancer Causes Control 1998, 9, 109–116.
  22. Preston-Martin, S.; Paganini-Hill, A.; Henderson, B.E.; Pike, M.C.; Wood, C. Case-control study of intracranial meningiomas in women in Los Angeles County, California. J. Natl. Cancer Inst. 1980, 65, 67–73.
  23. Preston-Martin, S.; Pogoda, J.M.; Schlehofer, B.; Blettner, M.; Howe, G.R.; Ryan, P.; Menegoz, F.; Giles, G.G.; Rodvall, Y.; Choi, N.W.; et al. An international case-control study of adult glioma and meningioma: The role of head trauma. Int. J. Epidemiol. 1998, 27, 579–586.
  24. Nelson, L.R.; Bulun, S.E. Estrogen production and action. J. Am. Acad. Dermatol. 2001, 45, S116–S124.
  25. Jialal, I.; Devaraj, S. Subcutaneous adipose tissue biology in metabolic syndrome. Horm. Mol. Biol. Clin. Investig. 2018, 33, 1–6.
  26. Little, R.B.; Madden, M.H.; Thompson, R.C.; Olson, J.J.; LaRocca, R.V.; Pan, E.; Browning, J.E.; Egan, K.M.; Nabors, L.B. Anthropometric factors in relation to risk of glioma. Cancer Causes Control 2013, 24, 1025–1031.
  27. Fantuzzi, G. Adipose tissue, adipokines, and inflammation. J. Allergy Clin. Immunol. 2005, 115, 911–919.
  28. Moore, S.C.; Rajaraman, P.; Dubrow, R.; Darefsky, A.S.; Koebnick, C.; Hollenbeck, A.; Schatzkin, A.; Leitzmann, M.F. Height, body mass index, and physical activity in relation to glioma risk. Cancer Res. 2009, 69, 8349–8355.
  29. Wiedmann, M.K.H.; Brunborg, C.; Di Ieva, A.; Lindemann, K.; Johannesen, T.B.; Vatten, L.; Helseth, E.; Zwart, J.A. The impact of body mass index and height on the risk for glioblastoma and other glioma subgroups: A large prospective cohort study. Neuro-Oncology 2017, 19, 976–985.
  30. Seliger, C.; Ricci, C.; Meier, C.R.; Bodmer, M.; Jick, S.S.; Bogdahn, U.; Hau, P.; Leitzmann, M.F. Diabetes, use of antidiabetic drugs, and the risk of glioma. Neuro-Oncology 2016, 18, 340–349.
  31. Liang, S.; Lv, G.; Chen, W.; Jiang, J.; Wang, J. Height and kidney cancer risk: A meta-analysis of prospective studies. J. Cancer Res. Clin. Oncol. 2015, 141, 1799–1807.
  32. Song, X.; Gong, X.; Zhang, T.; Jiang, W. Height and risk of colorectal cancer: A meta-analysis. Eur. J. Cancer Prev. 2018, 27, 521–529.
  33. Juul, A.; Bang, P.; Hertel, N.T.; Main, K.; Dalgaard, P.; Jørgensen, K.; Müller, J.; Hall, K.; Skakkebaek, N.E. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: Relation to age, sex, stage of puberty, testicular size, and body mass index. J. Clin. Endocrinol. Metab. 1994, 78, 744–752.
  34. Patil, S.S.; Railkar, R.; Swain, M.; Atreya, H.S.; Dighe, R.R.; Kondaiah, P. Novel anti IGFBP2 single chain variable fragment inhibits glioma cell migration and invasion. J. Neurooncol. 2015, 123, 225–235.
  35. Phillips, L.M.; Zhou, X.; Cogdell, D.E.; Chua, C.Y.; Huisinga, A.; Hess, K.R.; Fuller, G.N.; Zhang, W. Glioma progression is mediated by an addiction to aberrant IGFBP2 expression and can be blocked using anti-IGFBP2 strategies. J. Pathol. 2016, 239, 355–364.
  36. Dunlap, S.M.; Celestino, J.; Wang, H.; Jiang, R.; Holland, E.C.; Fuller, G.N.; Zhang, W. Insulin-like growth factor binding protein 2 promotes glioma development and progression. Proc. Natl. Acad. Sci. USA 2007, 104, 11736–11741.
  37. Sunderman, F.W. Nasal toxicity, carcinogenicity, and olfactory uptake of metals. Ann. Clin. Lab. Sci. 2001, 31, 3–24.
  38. Parent, M.E.; Turner, M.C.; Lavoué, J.; Richard, H.; Figuerola, J.; Kincl, L.; Richardson, L.; Benke, G.; Blettner, M.; Fleming, S.; et al. Lifetime occupational exposure to metals and welding fumes, and risk of glioma: A 7-country population-based case-control study. Environ. Health Glob. Access Sci. Source 2017, 16, 90.
  39. Sanders, T.; Liu, Y.; Buchner, V.; Tchounwou, P.B. Neurotoxic effects and biomarkers of lead exposure: A review. Rev. Environ. Health 2009, 24, 15–45.
  40. Liao, L.M.; Friesen, M.C.; Xiang, Y.B.; Cai, H.; Koh, D.H.; Ji, B.T.; Yang, G.; Li, H.L.; Locke, S.J.; Rothman, N.; et al. Occupational lead exposure and associations with selected cancers: The Shanghai men’s and women’s health study cohorts. Environ. Health Perspect. 2016, 124, 97–103.
  41. Caffo, M.; Caruso, G.; La Fata, G.; Barresi, V.; Visalli, M.; Venza, M.; Venza, I. Heavy Metals and Epigenetic Alterations in Brain Tumors. Curr. Genom. 2015, 15, 457–463.
  42. Bhatti, P.; Stewart, P.A.; Hutchinson, A.; Rothman, N.; Linet, M.S.; Inskip, P.D.; Rajaraman, P. Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors. Cancer Epidemiol. Biomark. Prev. 2009, 18, 1841–1848.
  43. Ahn, J.; Park, M.Y.; Kang, M.Y.; Shin, I.S.; An, S.; Kim, H.R. Occupational lead exposure and brain tumors: Systematic review and meta-analysis. Int. J. Environ. Res. Public Health 2020, 17, 3975.
  44. Rajaraman, P.; Stewart, P.A.; Samet, J.M.; Schwartz, B.S.; Linet, M.S.; Zahm, S.H.; Rothman, N.; Yeager, M.; Fine, H.A.; Black, P.M.; et al. Lead, genetic susceptibility, and risk of adult brain tumors. Cancer Epidemiol. Biomark. Prev. 2006, 15, 2514–2520.
  45. Merritt, R.L.; Foran, C.M. Influence of persistent contaminants and steroid hormones on glioblastoma cell growth. J. Toxicol. Environ. Health-Part A Curr. Issues 2007, 70, 19–27.
  46. Morrison, H.I.; Semenciw, R.M.; Morison, D.; Magwood, S.; Mao, Y. Brain cancer and farming in Western Canada. Neuroepidemiology 1992, 11, 267–276.
  47. Doğanlar, O.; Doğanlar, Z.B.; Kurtdere, A.K.; Chasan, T.; Ok, E.S. Chronic exposure of human glioblastoma tumors to low concentrations of a pesticide mixture induced multidrug resistance against chemotherapy agents. Ecotoxicol. Environ. Saf. 2020, 202, 110940.
  48. Kuan, A.S.; Green, J.; Kitahara, C.M.; De González, A.B.; Key, T.; Reeves, G.K.; Flou, S.; Balkwill, A.; Bradbury, K.; Liao, L.M.; et al. Diet and risk of glioma: Combined analysis of 3 large prospective studies in the UK and USA. Neuro-Oncology 2019, 21, 944–952.
  49. Nkondjock, A. Coffee consumption and the risk of cancer: An overview. Cancer Lett. 2009, 277, 121–125.
  50. Yang, C.S.; Wang, X.; Lu, G.; Picinich, S.C. Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance. Nat. Rev. Cancer 2009, 9, 429–439.
  51. Cavin, C.; Holzhaeuser, D.; Scharf, G.; Constable, A.; Huber, W.W.; Schilter, B. Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem. Toxicol. 2002, 40, 1155–1163.
  52. Kang, S.S.; Han, K.S.; Ku, B.M.; Lee, Y.K.; Hong, J.; Shin, H.Y.; Almonte, A.G.; Woo, D.H.; Brat, D.J.; Hwang, E.M.; et al. Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival. Cancer Res. 2010, 70, 1173–1183.
  53. Fang, M.Z.; Wang, Y.; Ai, N.; Hou, Z.; Sun, Y.; Lu, H.; Welsh, W.; Yang, C.S. Tea Polyphenol (-)-Epigallocatechin-3-Gallate Inhibits DNA Methyltransferase and Reactivates Methylation-Silenced Genes in Cancer Cell Lines. Cancer Res. 2003, 63, 7563–7570.
  54. Huber, W.W.; Scharf, G.; Nagel, G.; Prustomersky, S.; Schulte-Hermann, R.; Kaina, B. Coffee and its chemopreventive components Kahweol and Cafestol increase the activity of O6-methylguanine-DNA methyltransferase in rat liver-Comparison with phase II xenobiotic metabolism. Mutat. Res.-Fundam. Mol. Mech. Mutagen. 2003, 522, 57–68.
  55. Holick, C.N.; Smith, S.G.; Giovannucci, E.; Michaud, D.S. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiol. Biomark. Prev. 2010, 19, 39–47.
  56. Dubrow, R.; Darefsky, A.S.; Freedman, N.D.; Hollenbeck, A.R.; Sinha, R. Coffee, tea, soda, and caffeine intake in relation to risk of adult glioma in the NIH-AARP Diet and Health Study. Cancer Causes Control 2012, 23, 757–768.
  57. Creed, J.H.; Smith-Warner, S.A.; Gerke, T.A.; Egan, K.M. A prospective study of coffee and tea consumption and the risk of glioma in the UK Biobank. Eur. J. Cancer 2020, 129, 123–131.
  58. Cote, D.J.; Bever, A.M.; Wilson, K.M.; Smith, T.R.; Smith-Warner, S.A.; Stampfer, M.J. A prospective study of tea and coffee intake and risk of glioma. Int. J. Cancer 2020, 146, 2442–2449.
  59. Michaud, D.S.; Gallo, V.; Schlehofer, B.; Tjønneland, A.; Olsen, A.; Overvad, K.; Dahm, C.C.; Teucher, B.; Lukanova, A.; Boeing, H.; et al. Coffee and tea intake and risk of brain tumors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am. J. Clin. Nutr. 2010, 92, 1145–1150.
  60. Malerba, S.; Galeone, C.; Pelucchi, C.; Turati, F.; Hashibe, M.; La Vecchia, C.; Tavani, A. A meta-analysis of coffee and tea consumption and the risk of glioma in adults. Cancer Causes Control 2013, 24, 267–276.
  61. Galeone, C.; Malerba, S.; Rota, M.; Bagnardi, V.; Negri, E.; Scotti, L.; Bellocco, R.; Corrao, G.; Boffetta, P.; La Vecchia, C.; et al. A meta-analysis of alcohol consumption and the risk of brain tumours. Ann. Oncol. 2013, 24, 514–523.
  62. Baglietto, L.; Giles, G.G.; English, D.R.; Karahalios, A.; Hopper, J.L.; Severi, G. Alcohol consumption and risk of glioblastoma; evidence from the Melbourne collaborative cohort study. Int. J. Cancer 2011, 128, 1929–1934.
  63. And, A.M.; Mitsumori, K. Spontaneous Occurrence and Chemical Induction of Neurogenic Tumors in Rats—Influence of Host Factors and Specificity of Chemical Structure. Crit. Rev. Toxicol. 1990, 20, 287–310.
  64. Hurley, S.F.; McNeil, J.J.; Donnan, G.A.; Forbes, A.; Salzberg, M.; Giles, G.G. Tobacco smoking and alcohol consumption as risk factors for glioma: A case-control study in Melbourne, Australia. J. Epidemiol. Community Health 1996, 50, 442–446.
  65. Qi, Z.-Y.; Shao, C.; Yang, C.; Wang, Z.; Hui, G.-Z. Alcohol consumption and risk of glioma: A meta-analysis of 19 observational studies. Nutrients 2014, 6, 504–516.
  66. Cote, D.J.; Samanic, C.M.; Smith, T.R.; Wang, M.; Smith-Warner, S.A.; Stampfer, M.J.; Egan, K.M. Alcohol intake and risk of glioma: Results from three prospective cohort studies. Eur. J. Epidemiol. 2021, 36, 965–974.
  67. Samanic, C.M.; Cote, D.J.; Creed, J.H.; Stampfer, M.J.; Wang, M.; Smith-Warner, S.A.; Egan, K.M. Prospective study of sleep duration and glioma risk. Cancer Causes Control. 2021, 32, 1039–1042.
  68. Orešković, D.; Kaštelančić, A.; Raguž, M.; Dlaka, D.; Predrijevac, N.; Matec, D.; Matec, M.; Tomac, D.; Jeleč, V.; Marinović, T.; et al. The vicious interplay between disrupted sleep and malignant brain tumors: A narrative review. Croat. Med. J. 2021, 62, 376–386.
  69. Lissoni, P.; Meregalli, S.; Nosetto, L.; Barni, S.; Tancini, G.; Fossati, V.; Maestroni, G. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology 1996, 53, 43–46.
  70. Cutando, A.; López-Valverde, A.; Arias-Santiago, S.; De Vicente, J.; De Diego, R.G. Role of melatonin in cancer treatment. Anticancer Res. 2012, 32, 2747–2753.
  71. Martín, V.; García-Santos, G.; Rodriguez-Blanco, J.; Casado-Zapico, S.; Sanchez-Sanchez, A.; Antolín, I.; Rodriguez, C. Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death. Cancer Lett. 2010, 287, 216–223.
  72. Zheng, X.; Pang, B.; Gu, G.; Gao, T.; Zhang, R.; Pang, Q.; Liu, Q. Melatonin inhibits glioblastoma stem-like cells through suppression of EZH2-NOTCH1 signaling axis. Int. J. Biol. Sci. 2017, 132, 245–253.
  73. Ortner, D.; Tripp, C.H.; Komenda, K.; Dubrac, S.; Zelger, B.; Hermann, M.; Doppler, W.; Tymoszuk, P.Z.; Boon, L.; Clausen, B.E.; et al. Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis. Oncoimmunology 2016, 6, e1260215.
  74. Kale, A.; Sharma, A.; Stolzing, A.; Desprez, P.Y.; Campisi, J. Role of immune cells in the removal of deleterious senescent cells. Immun. Ageing 2020, 17, 16.
  75. Medzhitov, R. Origin and physiological roles of inflammation. Nature 2008, 454, 428–435.
  76. Murata, M. Inflammation and cancer. Environ Health Prev. Med. 2018, 23, 50.
  77. Meira, L.B.; Bugni, J.M.; Green, S.L.; Lee, C.W.; Pang, B.; Borenshtein, D.; Rickman, B.H.; Rogers, A.B.; Moroski-Erkul, C.A.; McFaline, J.L.; et al. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J. Clin. Investig. 2008, 118, 2516–2525.
  78. Liu, C.H.; Chen, Z.; Chen, K.; Liao, F.T.; Chung, C.E.; Liu, X.; Lin, Y.C.; Keohavong, P.; Leikauf, G.D.; Di, Y.P. Lipopolysaccharide-Mediated Chronic Inflammation Promotes Tobacco Carcinogen-Induced Lung Cancer and Determines the Efficacy of Immunotherapy. Cancer Res. 2021, 81, 144–157.
  79. D’Mello, C.; Le, T.; Swain, M.G. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J. Neurosci. 2009, 29, 2089–2102.
  80. Kore, R.A.; Abraham, E.C. Inflammatory cytokines, interleukin-1 beta and tumor necrosis factor-alpha, upregulated in glioblastoma multiforme, raise the levels of CRYAB in exosomes secreted by U373 glioma cells. Biochem. Biophys. Res. Commun. 2014, 453, 326–331.
  81. Hoesel, B.; Schmid, J.A. The complexity of NF-κB signaling in inflammation and cancer. Mol. Cancer 2013, 12, 86.
  82. Kim, S.; Domon-Dell, C.; Kang, J.; Chung, D.H.; Freund, J.-N.; Evers, B.M. Down-regulation of the tumor suppressor PTEN by the tumor necrosis factor-alpha/nuclear factor-kappaB (NF-kappaB)-inducing kinase/NF-kappaB pathway is linked to a default IkappaB-alpha autoregulatory loop. J. Biol. Chem. 2004, 279, 4285–4291.
  83. Teo, G.S.L.; Ankrum, J.A.; Martinelli, R.; Boetto, S.E.; Simms, K.; Sciuto, T.E.; Dvorak, A.M.; Karp, J.M.; Carman, C.V. Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-α-activated endothelial cells via both leukocyte-like and novel mechanisms. Stem Cells 2012, 30, 2472–2486.
  84. Guo, G.; Gong, K.; Ali, S.; Ali, N.; Shallwani, S.; Hatanpaa, K.J.; Pan, E.; Mickey, B.; Burma, S.; Wang, D.H.; et al. A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma. Nat. Neurosci. 2017, 20, 1074–1084.
  85. Nabors, L.B.; Suswam, E.; Huang, Y.; Yang, X.; Johnson, M.J.; King, P.H. Tumor Necrosis Factor α Induces Angiogenic Factor Up-Regulation in Malignant Glioma Cells: A Role for RNA Stabilization and HuR. Cancer Res. 2003, 63, 4181–4187.
  86. Tarassishin, L.; Casper, D.; Lee, S.C. Aberrant expression of interleukin-1β and inflammasome activation in human malignant gliomas. PLoS ONE 2014, 9, e103432.
  87. Tarassishin, L.; Lim, J.; Weatherly, D.B.; Angeletti, R.H.; Lee, S.C. Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression. J. Proteom. 2014, 99, 152–168.
  88. Soroceanu, L.; Kharbanda, S.; Chen, R.; Soriano, R.H.; Aldape, K.; Misra, A.; Zha, J.; Forrest, W.F.; Nigro, J.M.; Modrusan, Z.; et al. Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma. Proc. Natl. Acad. Sci. USA 2007, 104, 3466–3471.
  89. Tili, E.; Michaille, J.-J.; Wernicke, D.; Alder, H.; Costinean, S.; Volinia, S.; Croce, C.M. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc. Natl. Acad. Sci. USA 2011, 108, 4908–4913.
  90. Chiu, J.W.; Binte Hanafi, Z.; Chew, L.C.Y.; Mei, Y.; Liu, H. IL-1α Processing, Signaling and Its Role in Cancer Progression. Cells 2021, 10, 92.
  91. Melisi, D.; Niu, J.; Chang, Z.; Xia, Q.; Peng, B.; Ishiyama, S.; Evans, D.B.; Chiao, P.J. Secreted interleukin-1alpha induces a metastatic phenotype in pancreatic cancer by sustaining a constitutive activation of nuclear factor-kappaB. Mol. Cancer Res. 2009, 7, 624–633.
  92. Lu, T.; Tian, L.; Han, Y.; Vogelbaum, M.; Stark, G.R. Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways. Proc. Natl. Acad. Sci. USA 2007, 104, 4365–4370.
  93. Yeung, Y.T.; McDonald, K.L.; Grewal, T.; Munoz, L. Interleukins in glioblastoma pathophysiology: Implications for therapy. Br. J. Pharmacol. 2013, 168, 591–606.
  94. Sasaki, A.; Tamura, M.; Hasegawa, M.; Ishiuchi, S.; Hirato, J.; Nakazato, Y. Expression of interleukin-1beta mRNA and protein in human gliomas assessed by RT-PCR and immunohistochemistry. J. Neuropathol. Exp. Neurol. 1998, 57, 653–663.
  95. Griffin, B.D.; Moynagh, P.N. Persistent interleukin-1beta signaling causes long term activation of NFkappaB in a promoter-specific manner in human glial cells. J. Biol. Chem. 2006, 281, 10316–10326.
  96. Meini, A.; Sticozzi, C.; Massai, L.; Palmi, M. A nitric oxide/Ca2+/calmodulin/ERK1/2 mitogen-activated protein kinase pathway is involved in the mitogenic effect of IL-1beta in human astrocytoma cells. Br. J. Pharmacol. 2008, 153, 1706–1717.
  97. Paugh, B.S.; Bryan, L.; Paugh, S.W.; Wilczynska, K.M.; Alvarez, S.M.; Singh, S.K.; Kapitonov, D.; Rokita, H.; Wright, S.; Griswold-Prenner, I.; et al. Interleukin-1 regulates the expression of sphingosine kinase 1 in glioblastoma cells. J. Biol. Chem. 2009, 284, 3408–3417.
  98. Sharma, V.; Dixit, D.; Ghosh, S.; Sen, E. COX-2 regulates the proliferation of glioma stem like cells. Neurochem. Int. 2011, 59, 567–571.
  99. Yeung, Y.T.; Bryce, N.S.; Adams, S.; Braidy, N.; Konayagi, M.; McDonald, K.L.; Teo, C.; Guillemin, G.J.; Grewal, T.; Munoz, L. p38 MAPK inhibitors attenuate pro-inflammatory cytokine production and the invasiveness of human U251 glioblastoma cells. J. Neurooncol. 2012, 109, 35–44.
  100. Shan, Y.; He, X.; Song, W.; Han, D.; Niu, J.; Wang, J. Role of IL-6 in the invasiveness and prognosis of glioma. Int. J. Clin. Exp. Med. 2015, 8, 9114–9120.
  101. Tchirkov, A.; Khalil, T.; Chautard, E.; Mokhtari, K.; Véronèse, L.; Irthum, B.; Vago, P.; Kémény, J.-L.; Verrelle, P. Interleukin-6 gene amplification and shortened survival in glioblastoma patients. Br. J. Cancer 2007, 96, 474–476.
  102. Dhillon, A.S.; Hagan, S.; Rath, O.; Kolch, W. MAP kinase signalling pathways in cancer. Oncogene 2007, 26, 3279–3290.
  103. Crespo, S.; Kind, M.; Arcaro, A. The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis. JCMT 2016, 2, 80–89.
  104. Nicolas, C.S.; Amici, M.; Bortolotto, Z.A.; Doherty, A.; Csaba, Z.; Fafouri, A.; Dournaud, P.; Gressens, P.; Collingridge, G.L.; Peineau, S. The role of JAK-STAT signaling within the CNS. JAKSTAT 2013, 2, e22925.
  105. Baan, R.; Grosse, Y.; Lauby-Secretan, B.; El Ghissassi, F.; Bouvard, V.; Benbrahim-Tallaa, L.; Guha, N.; Islami, F.; Galichet, L.; Straif, K.; et al. Carcinogenicity of radio frequency electromagnetic fields. Lancet Oncol. 2011, 12, 624–626.
  106. Hardell, L.; Carlberg, M. Mobile phone and cordless phone use and the risk for glioma—Analysis of pooled case-control studies in Sweden, 1997–2003 and 2007–2009. Pathophysiology 2015, 22, 1–13.
  107. Villeneuve, P.J.; Momoli, F.; Parent, M.É.; Siemiatycki, J.; Turner, M.C.; Krewski, D. Cell phone use and the risk of glioma: Are case-control study findings consistent with Canadian time trends in cancer incidence? Environ. Res. 2021, 200, 111283.
  108. Cardis, E.; Deltour, I.; Vrijheid, M.; Combalot, E.; Moissonnier, M.; Tardy, H.; Armstrong, B.; Giles, G.; Brown, J.; Siemiatycki, J.; et al. Brain tumour risk in relation to mobile telephone use: Results of the INTERPHONE international case-control study. Int. J. Epidemiol. 2010, 39, 675–694.
  109. Olsson, A.; Bouaoun, L.; Auvinen, A.; Feychting, M.; Johansen, C.; Mathiesen, T.; Melin, B.; Lahkola, A.; Larjavaara, S.; Villegier, A.S.; et al. Survival of glioma patients in relation to mobile phone use in Denmark, Finland and Sweden. J. Neurooncol. 2019, 141, 139–149.
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