The cells of origin of sporadic schwannomas are transformed Schwann cells from cranial nerves, peripheral nerves, or nerve roots. The cells of origin of sporadic neurofibromas are a mixture of transformed Schwann cells, fibroblasts, and perineurial cells, although this remains controversial (Parisi and Mena 1993). Although the initial genesis of cellular neoplastic transformation is unknown in most cases (Rubinstein et al 1989; Salvati et al 1992), various contributory cytogenetic, chromosomal, and molecular biological events are discussed in this review. There is an association between acoustic schwannomas and prior radiation exposure, which has recently been corroborated by Schneider and colleagues. In a cohort of 3112 patients who had undergone irradiation as children (mean dose to posterior fossa 4.6 Gy), 43 (1.38%) developed an acoustic schwannoma, with a mean latency of 38.3 years. The relative risk was 1.14 per Gy of exposure (Schneider et al 2008). In a review of 90 patients with vestibular schwannoma and 86 controls, Muscat and colleagues studied the relative risk of cellular telephone usage (Muscat et al 2002). The relative risk was 0.9 (p = 0.07) and did not vary significantly based on the frequency, duration, or lifetime hours of use. A more recent review of cell phone use and incidence of vestibular schwannoma suggested a trend toward a higher incidence, but it did not reach a significant level (Hardell et al 2003). A follow-up study by Hardell and colleagues evaluating acoustic schwannoma patients noted an increased odds ratio for tumor development in those with a greater than 15-year latency period (Hardell et al 2005). However, these data were based on a cohort of only 84 patients and need further validation. In a larger study of 678 patients with acoustic schwannoma and 3553 controls, Schoemaker and colleagues noted an overall odds ratio of 0.9 (Schoemaker et al 2005). For patients with cumulative cell phone usage of 10 years or more, there was an increase in the odds ratio to 1.8. Further long-term epidemiological studies are needed to evaluate the use of cell phones (Welling et al 2007). A meta-analysis of published data on the use of cell phones and brain tumor risk shows an increased odds ratio (2.4) for the risk of ipsilateral acoustic schwannomas for those with a latency of use of greater than or equal to 10 years (Hardell et al 2008). The odds ratio was only 1.2 for development on the contralateral side. A recent large study from Sweden evaluated the relative risk of occupational exposure to 50 Hz magnetic fields and the development of acoustic schwannomas (Forssen et al 2006). They reviewed the records of 793 cases and 101,762 random controls for time-weighted average, peak values, and rate of change of magnetic field exposure. The results did not support an association between low-frequency magnetic field exposure and an increased risk of acoustic schwannoma.
Three meta-analyses have been published addressing the issue of cell phone and cordless phone use and the risk of a brain tumor (Hardell and Carlberg 2009; Han et al 2009; Khurana et al 2009). In the studies by Khurana and colleagues and Hardell and Carlberg, the overall risk for brain tumors was analyzed, whereas the focus was on acoustic schwannomas in the study by Han and colleagues. Hardell and Carlberg and Khurana and colleagues analyzed all of the published studies using long-term epidemiological data, with a minimum usage of 10 years (Hardell and Carlberg 2009; Khurana et al 2009). The data suggest that using a cell phone or cordless phone for greater than 10 years approximately doubles the risk for being diagnosed with an ipsilateral brain tumor (overall estimate odds ratio 1.6 to 1.9). The increased risk applies to astrocytomas and acoustic schwannomas, but not to meningiomas. The conclusions were similar in the study by Han and colleagues, which noted an increased odds ratio of 2.4 for developing an ipsilateral acoustic schwannoma in patients using cell phones for at least 10 years (Han et al 2009).
A recent epidemiological study from Sweden reviewed the records of 793 patients with vestibular schwannomas and correlated them with occupational and potential occupational exposures (Prochazka et al 2010). They noted an increased odds ratio for exposure to mercury (OR 2.9) and benzene (OR 1.8), as well as a 3-fold increased risk for females working as tailors and dressmakers. The risk for tumor development did not appear to be related to socioeconomic status.
Three more studies have been recently published assessing the risk of cell phone use and the development of brain tumors. Two studies were specific to vestibular schwannoma and evaluated patient cohorts in Europe (INTERPHONE Study Group 2011; Schuz et al 2011). In the study by Schuz and colleagues, 2 Danish nationwide cohorts totaling 2.9 million subjects were evaluated for cell phone use and risk of vestibular schwannoma (Schuz et al 2011). An increased incidence for schwannoma was not detectable. Furthermore, of the tumors that did develop, they were not larger than expected or more likely to be on the right side of the head (where most subjects used their phone). In the INTERPHONE Study Group report, 1105 patients with newly diagnosed vestibular schwannomas were compared to 2145 case-matched controls and assessed for past mobile phone use (INTERPHONE Study Group 2011). The OR for a vestibular schwannoma with ever using a cell phone was 0.85, whereas the OR for more than 10 years of cell phone usage was 0.76. In addition, no trends were noted for subjects with increasing cumulative call time or number of calls. In the most recent meta-analysis on the topic, Repacholi and colleagues reviewed the published data for a link between cell phone use and the risk for developing brain cancer or other head and neck tumors (Repacholi et al 2012). The data did not show a statistically significant increase in risk (defined as P < 0.05) for brain cancer or head and neck tumors.