Cellphone use, thyroid cancer and genetic susceptibility study — fact or fiction ???

From time to time, these GEITP pages tackle a controversial topic, and (sadly) this is one of those times. ☹ The International Agency for Research on Cancer (IARC) in 2011 classified radiofrequency radiation (RFR) — emitted from cell-phones — as a “possible human carcinogen (Group 2B)”, … on seriously limited evidence from humans (IARC Working Group, 2013). One cohort study (in 2006) and five case-control studies (between 2000 and 2011) were evaluated. Brain tumors (including glioma, acoustic neuroma, and meningioma) were evaluated in these studies. TWO of the six studies suggested “an increased risk of brain tumors” in people with the highest cumulative cell-phone usage. Although these studies were admitted to being “vulnerable to methodological limitations and possible biases” (such as no appropriate evidence-based metric for cell-phone use) — the working group nonetheless decided that “positive associations have been observed between exposure to RFR and glioma, and between RFR exposure and acoustic neuroma“ (IARC Working Group, 2013). The majority of the group members agreed that “positive associations in these studies could not be dismissed”, and therefore “it was appropriate to classify RFR as a Group 2B carcinogen.”

Since 2011, further studies have offered additional suggestive evidence on “the carcinogenicity of RFR.” In 2018, the National Toxicology Program (NTP) concluded that “there was clear evidence to support an association between cell-phone RFR exposure and tumors of heart and brain in male rats; these findings were confirmed by another animal study from the (controversial) Ramazzini Institute (in Bologna, Italy) [this institute has promoted an association between glyphosate and cancer in rats]. However, these animal studies are compounded by the level of RFR dosage required to cause the malignancies. Nine additional (case-control) population studies — (published since the IARC 2013 classification) — concluded that “long-term cell-phone use was associated with increased risk of brain tumors.” However, two cohort studies were unable to confirm any such association.

Authors [see attached article] examined the “genetic association” between cell-phone use and thyroid cancer by studing 440 cancer cases and 465 controls, and “genotyping for 823 single-nucleotide variants (SNVs) in 176 genes.” “Using multivariate unconditional logistic regression models,” authors found ten SNVs having “P-values of <0.01 for interaction in all thyroid cancers.” Whereas no association with RFR was found “in the homozygote groups,” the “variant group (heterozygotes and rare homozygotes for these ten SNVs) showed odds-ratio (OR) values (for RFR associated with thyroid cancer) between 1.59 and 2.64 [see the paper for details] — sadly with OR confidence intervals (C.I.s) sometimes as weak as 1.01. Authors claim that “their findings provide more evidence for the RFR carcinogenic group classification by showing an association with cell-phone use and thyroid cancer risk.” The study represents an excellent example of a Type I Error in statistics — a false positive (i.e. the test result incorrectly indicates that a particular condition, or attribute, is present, but it is not true). ☹ Authors must compare each SNV against the entire human haploid genome containing ~3 billion nucleotides. Thyroid cancer is one of the many multifactorial traits — so often stressed in these GEITP pages — meaning the trait reflects the contribution of: [a] hundreds if not thousands of ‘small-effect’ genes; [b] epigenetic factors (RNA interference, DNA methylation, histone modifications, chromatin remodeling); [c] environmental effects (which in this case would include, among others, RFR from cell-phones); [d] endogenous influences (e.g. cardiopulmonary or renal disease in each patient); and even [e] each individual’s unique microbiome. If these authors had discovered one or more SNVs showing true significance (P-value of <5.0e–08, also written as <5.0 x 10–8) — then this publication might have meant something. As it stands, this study is 100% bogus and should never have been published (yet, findings such as these often appear in news media reports). ☹ DwN Environ Res Jan 2020; 182: 1090132

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