The epidemiology of glioma in adults: a "state of the science" review

This is a wide-ranging and comprehensive study.1 However, the section “Nonionizing Radiation: Cellular Phones” has serious deficiencies. It cites 3 incidence time trend studies,2–4 2 cohort studies,5,6 and 1 case control study.7 Late ascertainment and poor histological concordance are common accuracy problems. Late ascertainment results in an underestimation of incidence rates in recently reported years. A paper reported: “Results: Initial incidence case counts … accounted for only 88%–97% of … final counts; it would take 4–17 years for 99% or more of the cancer cases to be reported.”8 Another study reported that the histological concordance by 4 neuropathologists reviewing gliomas was “52% all 4 reviewers, any 3 reviewers, 60%; 2 reviewers, 70%.”9 The study by Deltour and colleagues2 reported that glioma rates were stable among the 40–59 age group from 1979 to 2008.2 The Ostrom authors1 failed to report a significant increase, ages 20–79, annual percent change (APC) = 0.4%, 95% CI = 0.1%–0.6% in men and APC = 0.3%, 95% CI = 0.1%–0.5% in women.2 It received funding via a “firewall” from the cellphone companies Telia-Sonera, Telenor, and Ericsson.10 During the years of this study (1979 to ∼1994; 53% of the duration), cellphones did not exist or the prevalence was very low; in 1998 the prevalence was 44%; by 2005 prevalence had reached 100%. With incidence trends over a 30-year period where in most of the years there was almost no cellphone use and with only 3 years of 100% prevalence, how can one conclude whether or not cellphone use was affecting incidence? The US study by Little and colleagues3 was for the years 1992–2008.3 In 1992 cellphone prevalence was 1% and by 2008 it was 84%.11 A 2013 report noted that the Veterans Administration hospitals had ceased from 2005 to 2014 to report cancer cases diagnosed among military veterans.12 The result was that 3%–8% of all male cancer cases were missing. In 1992, only 1% of the population were using cellphones, whereas by 2008, use was at 84%. With 3%–8% of male cancers not reported, combined with late ascertainment, how could a change in glioma incidence rates be expected? In spite of these issues, Little et al reported a significantly increased APC in temporal lobe glioma, APC = 0.73%, 95% CI = 0.23%–1.23%. The temporal lobe absorbs the largest proportion of cellphone radiation of any anatomic region of the brain.13 The title of the third incidence time trend study cited, “Changes in Brain Glioma Incidence and Laterality Correlates With Use of Mobile Phones—a Nationwide Population Based Study” (emphasis added),4 is in direct contradiction to the assertions in the deficient section. A US paper examined cancer incidence across 3 cancer registries for the years 1992–2006.14 It reported: “Data from 3 major cancer registries demonstrate increased [APC] incidences of GBMs in the frontal lobe, temporal lobe, and cerebellum.” These 3 anatomic regions absorb between 81% (900 MHz) and 86% (1800 MHz) of all the cellphone radiation absorbed by the brain.13 An Australian paper with 2000–2008 data,15 though cited in the Ostrom study,1 was not cited for its time trend results, brain cancer APC = 3.9%, 95% CI = 2.4–5.5.15 The same team reported: “A significant increasing incidence in glioblastoma multiforme … was observed in the study period [APC = 2.5%, 95% CI = 0.4–4.6], particularly after 2006.”16 For the years 2003–2012 the Danish Cancer Registry reported an increased incidence of male and female brain cancers of 41.2% and 46.1%, respectively.17 The Ostrom study cited 2 cohort studies as evidence that cellphone use is not a risk for glioma.5,6 For rare diseases, case control studies are essential. Cohort studies are incapable of determining risks.18 It is axiomatic that absence of evidence is not evidence of absence. Both studies found significant reduced risks for various cancers. A single case control study was cited, noting that its odds ratios (ORs) “were markedly elevated in all categories of use.”7 The Hardell team's significant findings are consistent with what would be expected if wireless phones (cell and cordless) were causing brain cancer: Another study reported brain cancer risk with 1640+ hours of cellphone use compared with <5 hours of use, OR = 1.82, 95% CI = 1.15–2.89; and for 10+ years since use compared with 1–1.9 years since first use, OR = 2.18, 95% CI = 1.43–3.31.23 The higher the cumulative hours of use, the higher the risk.7,19 The longer the time since first use, the higher the risk.7,19–21 The higher the radiated power, the higher the risk.7,19–21 Ipsilateral risk is higher than contralateral risk.7,19,20,22 The CERENAT study reported “heavy mobile phone use” (≥896 hours), OR = 2.89, 95% CI = 1.41–5.93; with 5+ years since first use, OR = 5.30, 95% CI = 2.12–13.23, P<.001; and for use exclusively in urban areas, OR = 8.20, 95% CI = 1.37–49.07.24 In conclusion, the authors' statement that the “evidence published since the IARC monograph in 2011 does not support an association between cellular phone use and the risk of glioma in adults1” requires revision.