USA: Incidentie hersentumoren in VS vergeleken met epidemiologische studies. (Upd. + reactie)

dinsdag, 20 maart 2012 - Categorie: Onderzoeken

Geplaatst 13 maart 2012
Update met deskundige analyse prof. Kundi 20 dec 2012

Bron: British Medical Journal 2012 Mar 8; 344: e1147.

Mobile phone use and glioma risk: comparison of epidemiological study results with incidence trends in the United States.

Little MP, Rajaraman P, Curtis RE, Devesa SS, Inskip PD, Check DP, Linet MS.

Radiation Epidemiology Branch, National Cancer Institute, Rockville, MD 20852-7238, USA.

OBJECTIVE: In view of mobile phone exposure being classified as a possible human carcinogen by the International Agency for Research on Cancer (IARC), we determined the compatibility of two recent reports of glioma risk (forming the basis of the IARC's classification) with observed incidence trends in the United States.

DESIGN: Comparison of observed rates with projected rates of glioma incidence for 1997-2008. We estimated projected rates by combining relative risks reported in the 2010 Interphone study and a 2011 Swedish study by Hardell and colleagues with rates adjusted for age, registry, and sex; data for mobile phone use; and various latency periods.

SETTING: US population based data for glioma incidence in 1992-2008, from 12 registries in the Surveillance, Epidemiology, and End Results (SEER) programme (Atlanta, Detroit, Los Angeles, San Francisco, San Jose-Monterey, Seattle, rural Georgia, Connecticut, Hawaii, Iowa, New Mexico, and Utah).

PARTICIPANTS: Data for 24 813 non-Hispanic white people diagnosed with glioma at age 18 years or older.

RESULTS: Age specific incidence rates of glioma remained generally constant in 1992-2008 (-0.02% change per year, 95% confidence interval -0.28% to 0.25%), a period coinciding with a substantial increase in mobile phone use from close to 0% to almost 100% of the US population. If phone use was associated with glioma risk, we expected glioma incidence rates to be higher than those observed, even with a latency period of 10 years and low relative risks (1.5). Based on relative risks of glioma by tumour latency and cumulative hours of phone use in the Swedish study, predicted rates should have been at least 40% higher than observed rates in 2008. However, predicted glioma rates based on the small proportion of highly exposed people in the Interphone study could be consistent with the observed data. Results remained valid if we used either non-regular users or low users of mobile phones as the baseline category, and if we constrained relative risks to be more than 1.

CONCLUSIONS: Raised risks of glioma with mobile phone use, as reported by one (Swedish) study forming the basis of the IARC's re-evaluation of mobile phone exposure, are not consistent with observed incidence trends in US population data, although the US data could be consistent with the modest excess risks in the Interphone study.

Voor het originele abstract zie: .

Op 20 maart 2012 verscheen in de British Medical Journal onderstaand commentaar van prof. Kundi, epidemioloog aan de medische universiteit Wenen:

Mobile phone use and glioma risk: comparison of epidemiological study results with incidence trends in the United States

The article by Little et al. is an example of the review process still having much room for improvement. Never should it have passed review without substantial changes. There are too many errors, omissions, and imprecisions to mention all of them in this short commentary, just a few comments:

• The essential figure 2, according to its legend showing “Observed and projected rates (95% CI) of malignant glioma in non-Hispanic white people, by latency period and various assumed levels of relative risk associated with ever using a phone”, will even a student of cancer epidemiology immediately recognize as either faulty or showing something else. In fact it shows the estimated glioma rate in 60-64 year old males from Los Angeles. Not exactly what one expects from the legend.

• But what it shows reveals another problem with this paper: it intends to show that the observed trend in incidences of glioma in the US is incompatible with the results of the Swedish case-control studies of the Hardell group, but the method of calculation of the projected rates is flawed on the one hand, and incompatible with what is known about mobile phone use on the other. The authors applied a decomposition of the base rate (the rate in 60-64 year old males from Los Angeles) into the expected fraction of mobile phone users with a duration of use of 1-4, 5-10, >10 years and non-users or users of less than one year. For each of these population segments the odds-ratios reported by the Hardell (and Interphone) group are interpreted as estimates of the relative risk and are used as multipliers for the population fractions (by the way, the formula A2 in the appendix is wrong as in the second term under the square brackets the proportion of the population expected to use a mobile phone longer than 10 years before the year y of interest, CP(y-10), is subtracted twice as this segment is already contained in CP(y-5)).

Why is this method flawed? First of all, the effect of a risk from mobile phone use at the population level is a shift of the age-incidence curve, i.e. the diagnosis occurs at an earlier age. Because age and mobility are strongly related it is a problem if registries for selected regions only are used since the population base is not stable and hence the risk sets are variable. Furthermore, the fractions of mobile phone use cannot be applied invariably for all segments of the population. Inskip et al. (2001) as well as Muscat et al. (2000, 2002) have shown that (at least during the late 1990s) there is a huge difference in the fraction of mobile phone users between age groups and between males and females and also occupation played an important role. As the mobile phone penetration rate becomes larger these differences will become smaller. This should have been modeled as well as regional differences in mobile phone penetration rates and the increasing proportion of users of more than one mobile phone.

• If such a method is applied and all age groups are considered and not only those 60-64 years of age, there is still a small increase predicted by the odds-ratios of the Hardell group, but much less pronounced compared to those shown in figure 2 of Little et al. and very close to the rates reported by CBTRUS for 2004-2007. Unfortunately CBTRUS data cannot be easily applied for long-term trend estimates because the coverage rate increased strongly over the last decades.


CBTRUS. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2007. Central Brain Tumor Registry of the United States, Hinsdale, IL.

Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Shapiro WR, Selker RG, Fine HA, Black PM, Loeffler JS, Linet MS. Cellular-telephone use and brain tumors. N Engl J Med. 2001;344(2):79-86.

Muscat JE, Malkin MG, Shore RE, Thompson S, Neugut AI, Stellman SD, Bruce J. Handheld cellular telephones and risk of acoustic neuroma. Neurology. 2002;58(8):1304-6.

Muscat JE, Malkin MG, Thompson S, Shore RE, Stellman SD, McRee D, Neugut AI, Wynder EL. Handheld cellular telephone use and risk of brain cancer. JAMA. 2000;284(23):3001-7

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