Monday, April 06, 2015

Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register

Joel's comments: This study examined the national inpatient registry in Sweden and found that many brain and central nervous system tumors of unknown type are not reported to the cancer registry. The annual percentage change for this type of tumor increased from 0.2% from 1998 to 2007 to 4.25% from 2007 to 2013, or from about 8 per 100,000 patients in 2007 to more than 10 per 100,000 patients in 2013.

The study is highly important because scientists from the Interphone study, WHO, and SCENIHR have repeatedly cited the flat brain tumor incidence trend from the Swedish cancer registry to dismiss the Hardell group's case-control studies which found increased glioma risk associated with wireless phone use. The denialists argue that if glioma risk doubles after ten years, then why aren't we seeing the increase in the cancer registry?  Apparently, many diagnosed cases are not being reported to the cancer registry; hence, the Swedish cancer registry data may not be reliable for tracking brain tumor incidence.


Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register

Hardell L, Carlberg M. Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register. International Journal of Environmental Research and Public Health. 2015; 12(4):3793-3813.


Radiofrequency emissions in the frequency range 30 kHz–300 GHz were evaluated to be Group 2B, i.e., “possibly”, carcinogenic to humans by the International Agency for Research on Cancer (IARC) at WHO in May 2011. The Swedish Cancer Register has not shown increasing incidence of brain tumours in recent years and has been used to dismiss epidemiological evidence on a risk.

In this study we used the Swedish National Inpatient Register (IPR) and Causes of Death Register (CDR) to further study the incidence comparing with the Cancer Register data for the time period 1998–2013 using joinpoint regression analysis.

In the IPR we found a joinpoint in 2007 with Annual Percentage Change (APC) +4.25% (95% CI: +1.98, +6.57%) during 2007–2013 for tumours of unknown type in the brain or CNS. In the CDR joinpoint regression found one joinpoint in 2008 with APC during 2008–2013 +22.60% (95% CI: +9.68, +37.03%).

These tumour diagnoses would be based on clinical examination, mainly CT and/or MRI, but without histopathology or cytology. No statistically significant increasing incidence was found in the Swedish Cancer Register during these years. We postulate that a large part of brain tumours of unknown type are never reported to the Cancer Register. Furthermore, the frequency of diagnosis based on autopsy has declined substantially due to a general decline of autopsies in Sweden adding further to missing cases.

We conclude that the Swedish Cancer Register is not reliable to be used to dismiss results in epidemiological studies on the use of wireless phones and brain tumour risk.
Open Access Paper:

There has been a rapid increase in the use of both mobile and cordless phones during the last two decades. Worldwide, an estimate of 6.9 billion mobile phone subscriptions were reported at the end of 2014 by the International Telecommunication Union [1]. 
The Nordic countries were among the first in the world to widely adopt wireless telecommunications technology ...

The real increase in the use and exposure to radiofrequency electromagnetic fields (RF-EMF) from wireless phones (mobile phones and cordless phones) in most countries has occurred since the 1990s. The anatomical distribution to the human body of RF emissions depends on e.g., if the wireless phone is handheld or not, type of tissue and age [2,3,4]. The user may also be exposed to extremely low frequency (ELF)-EMF from the battery [5,6].

It has been suggested that overall incidence data on brain tumours for countries may be used to qualify or disqualify the association between mobile phones and brain tumours observed in case-control studies. During recent years such opinions have been published by different study groups. However, it must be stressed that descriptive epidemiology with no individual exposure data is of less value than results in analytical epidemiology such as case-control studies [17].
The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) at EU published on 12 December 2013 a “Preliminary opinion on potential health effects of exposure to electromagnetic fields (EMF)” [23]. The committee’s conclusion was that “Based on the most recent cohort and incidence time trend studies, it appears that the evidence for an increased risk of glioma became weaker while the possibility of an association of RF EMF exposure with acoustic neuroma remains open”. The conclusion in the final report was that “The results of cohort and incidence time trend studies do not support an increased risk for glioma while the possibility of an association with acoustic neuroma remains open” (Dated 20 January 2015) [24].
In September, 2014 WHO published the draft: Radio Frequency fields: Environmental Health Criteria Monograph [25]. The results by Deltour et al. [20] on brain tumour incidence in the Nordic countries were cited without further analysis of the findings: “if the risk increases that were reported in a few case-control studies to be associated with mobile phone use were real, they would have resulted in a detectable increase in the glioma incidence in the Nordic countries”.
It is obvious that descriptive data from the Swedish Cancer Register on brain tumour incidence are increasingly used to dismiss results in analytical epidemiology on the association between brain tumours and use of mobile and cordless phones. An increasing number of patients with brain tumour of “unknown type” based on patient register data was recently reported [26].
Inpatient Registry

Benign Meningeal Tumours (CNS): According to the IPR, AAPC increased slightly during 1998–2013, although not statistically significant, see Table 1. No joinpoint was detected.

Benign Tumour in the Brain or CNS: A slight decrease of AAPC was seen both in men and women in the IPR. The result was not statistically significant and no joinpoint was detected ...

Tumour of Unknown Type in the Meninges (CNS): A statistically significant decreasing AAPC in IPR was found for both genders during 1998–2003, Table 1. A joinpoint was found in 2003 for men. The results were based on rather low numbers.

Tumour of Unknown Type in the Brain or CNS
: Figure 1 shows number of patients per 100,000 inhabitants according to the IPR for both genders combined, all ages during 1998–2013. One joinpoint was detected in 2007 (1998–2007: APC +0.17%, 95% CI −1.01, +1.37%; 2007–2013: APC +4.25%, 95% CI +1.98, +6.57%). AAPC for the whole time period was +1.78%, 95% CI +0.76, +2.81%, Table 1. The trends were similar in men and women although for women the joinpoint was detected in 2008.

Malignant Brain Tumours: In IPR AAPC for malignant brain tumours was calculated to −0.31%, 95% CI −0.97, +0.36% (men and women combined) for the time period 1998–2013. Two joinpoints were detected, 2001 and 2006 (1998–2001: APC −3.60%, 95% CI −5.96, −1.17%; 2001–2006: APC +2.11%, 95% CI +0.52, +3.72%, and 2006–2013: APC −0.58%, 95% CI −1.23, +0.08%, respectively).

Cancer Registry

Brain Tumours (Including Brain, Meninges, CNS Nerves):
 Trends in age-standardized incidence rates per 100,000 were calculated. For the time period 1998–2013 AAPC was calculated to +0.06%, 95% CI −0.57, +0.69% in men, and to +0.17%, 95% CI −0.60, +0.95% in women. No joinpoint was detected ...

Mobile Phone Communications

There was an increase from 2004 due to lower price from March 2003 to the end of 2005. The cost for cheapest use was reduced by 38% for the average user [34]. The number of patients per 100,000 with brain tumour of unknown type, D43, in IPR and age-standardized rate of death rate per 100,000 in CDR started to increase a few years later than 2004, see Figure 5 and Figure 6.

We found a higher OR with short latency, and after some decline an increasing risk with longer latency (non-linearity, p = 0.01). The results indicate both an early effect in glioma genesis (initiation), but also a late effect in carcinogenesis (promotion/progression). The increasing rates of brain tumours in Figure 5 and Figure 6 may be explained by a late effect in carcinogenesis (promotion/progression) from exposure to RF-emissions from mobile phone use.

The main finding in this study was increasing rates of brain tumours of unknown type in the central nervous system (D43). One might speculate that these tumours represent metastases to the brain of tumours at other sites in the body. This is however unlikely since these are coded as tumours located at the original site. In the IPR the number per 100,000 patients was relatively stable until 2007 when a joinpoint was detected for men and 2008 for women. After that year the rate increased statistically significant yearly with almost 5% in men and more than 4% in women. The tumour may be calculated several times if registered during several years. It is however unlikely that this explains the clear change of the rate in Figure 1 and of course not the increasing death rate in Figure 2. Also it must be stressed that the same diagnosis is not included several times in the IPR during the same year if the person moves from one county to another, for example from a county hospital to a university hospital. All counties in Sweden are included in the same register and only unique personal id-numbers are used.

It is striking that the yearly age-standardized death rates per 100,000 inhabitants increased in the CDR from 2008 for brain tumours of unknown type (D43), the joinpoint in both men and women. The yearly statistically significant increase was 24% in men and 20% in women. For the time period 1998–2008 the rate decreased statistically significantly in both men, 9%, and in women, 6%. These results indicate that the increasing rate in the IPR is caused by inpatients with a malignant brain tumour with short survival, since the total (men and women) joinpoint shifted in 2007 in IPR, but one year later, 2008, in CDR.

Quality control has shown that brain tumours are among the tumour types with large deficits in the reporting to the Cancer Register [43]. In a sample from 1998 of 202 medical records 93 cancer cases were identified that should have been reported to the Cancer Register. Of these 30% had a cancer diagnosis verified by histology (19%) or cytology (11%) whereby the pathology departments around Sweden had missed to report these cases. For 70% the cancer diagnosis was based on clinical examination only and were thus not reported to the Cancer Register by the clinical departments.

Incidence data on brain tumours in the Swedish Cancer Registry are used to dismiss the increased risk associated with use of wireless phones in our studies [18,20]; see also above SCENIHR and WHO [above]. Interestingly this study showed increasing rates of brain tumours of unknown type with joinpoint 2007 (all). This may be in accordance with our findings of increased glioma risk associated with use of wireless phones. In fact this increase is some years after increasing number of out-going mobile minutes. These data do also fit with our restricted cubic spline plot with a late effect in carcinogenesis [32], see also Appendix II in the Interphone study [12]. Tumour promotion by RF-EMF exposure was reported in 2010 in a study on mice [46]. These findings were recently replicated [47] and add to the relevance of our results. An even more increasing rate of brain tumours in the future may be predicted based on these data. In contrast the data do not show a statistically significant increase of the rate of meningioma, a tumour type that has no consistent association with use of wireless phones [8,48]. Only ionizing radiation is since before an established risk factor for brain tumours. However there are no data indicating increasing such exposure in the Swedish population that may explain our results.

In summary this study shows that the Swedish Cancer Register is not reliable to be used to dismiss results in epidemiological studies on the use of wireless phones and brain tumour risk and should not be used as reference for such statements. In fact both the IPR and CPR indicate a considerable underreporting to the Cancer Register during recent years. Record linkage between IPR, CDR and the Swedish Cancer Register should be the next step to further elucidate this underreporting.

Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley

Electromagnetic Radiation Safety

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