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    Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study
    (Elsevier Ltd, 2022-02) Castaño-Vinyals G; Sadetzki S; Vermeulen R; Momoli F; Kundi M; Merletti F; Maslanyj M; Calderon C; Wiart J; Lee A-K; Taki M; Sim M; Armstrong B; Benke G; Schattner R; Hutter H-P; Krewski D; Mohipp C; Ritvo P; Spinelli J; Lacour B; Remen T; Radon K; Weinmann T; Petridou ET; Moschovi M; Pourtsidis A; Oikonomou K; Kanavidis P; Bouka E; Dikshit R; Nagrani R; Chetrit A; Bruchim R; Maule M; Migliore E; Filippini G; Miligi L; Mattioli S; Kojimahara N; Yamaguchi N; Ha M; Choi K; Kromhout H; Goedhart G; 't Mannetje A; Eng A; Langer CE; Alguacil J; Aragonés N; Morales-Suárez-Varela M; Badia F; Albert A; Carretero G; Cardis E
    In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.
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    Exposure to drinking water trihalomethanes and nitrate and the risk of brain tumours in young people
    (Elsevier Inc, 2021-09) Zumel-Marne A; Castaño-Vinyals G; Alguacil J; Villanueva CM; Maule M; Gracia-Lavedan E; Momoli F; Krewski D; Mohipp C; Petridou E; Bouka E; Merletti F; Migliore E; Piro S; Ha M; 't Mannetje A; Eng A; Aragones N; Cardis E
    Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10-24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010-2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08-1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91-3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations.
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    Heirarchical regression for multiple comparisons in a case-control study of occupational risks for lung cancer.
    (Public Library of Science, 11/06/2012) Corbin M; Richiardi L; Vermeulen R; Kromhout H; Merletti F; Peters S; Simonato L; Steenland K; Pearce NE; Maule M
    Background Occupational studies often involve multiple comparisons and therefore suffer from false positive findings. Semi-Bayes adjustment methods have sometimes been used to address this issue. Hierarchical regression is a more general approach, including Semi-Bayes adjustment as a special case, that aims at improving the validity of standard maximum-likelihood estimates in the presence of multiple comparisons by incorporating similarities between the exposures of interest in a second-stage model. Methodology/Principal Findings We re-analysed data from an occupational case-control study of lung cancer, applying hierarchical regression. In the second-stage model, we included the exposure to three known lung carcinogens (asbestos, chromium and silica) for each occupation, under the assumption that occupations entailing similar carcinogenic exposures are associated with similar risks of lung cancer. Hierarchical regression estimates had smaller confidence intervals than maximum-likelihood estimates. The shrinkage toward the null was stronger for extreme, less stable estimates (e.g., “specialised farmers”: maximum-likelihood OR: 3.44, 95%CI 0.90–13.17; hierarchical regression OR: 1.53, 95%CI 0.63–3.68). Unlike Semi-Bayes adjustment toward the global mean, hierarchical regression did not shrink all the ORs towards the null (e.g., “Metal smelting, converting and refining furnacemen”: maximum-likelihood OR: 1.07, Semi-Bayes OR: 1.06, hierarchical regression OR: 1.26). Conclusions/Significance Hierarchical regression could be a valuable tool in occupational studies in which disease risk is estimated for a large amount of occupations when we have information available on the key carcinogenic exposures involved in each occupation. With the constant progress in exposure assessment methods in occupational settings and the availability of Job Exposure Matrices, it should become easier to apply this approach.