Anders Ahlbom

Calculating measures of biological interaction.

An editorial in this issue explains that the degree of biological interaction between risk factors is measured as the deviation from additivity by the corresponding disease rates and not for example as deviation from multiplicativity. It is the purpose of this article to describe how a logistic regression model, or a Cox regression model, can be defined in order to produce the output that is needed for assessment of biological interaction. We will also demonstrate how common software can be programmed to deliver this output. Finally, we show how this output can be used as input in an Excel sheet that is set up to calculate the measures of biological interaction to be used for the assessment.

Genome-wide association study identifies five susceptibility loci for glioma.

To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 × 10−17), 8q24.21 (rs4295627, CCDC26; P = 2.34 × 10−18), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 × 10−15), 20q13.33 (rs6010620, RTEL1; P = 2.52 × 10−12) and 11q23.3 (rs498872, PHLDB1; P = 1.07 × 10−8). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

A pooled analysis of magnetic fields and childhood leukaemia

Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 μT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures ≥ 0.4 μT the estimated summary relative risk was 2.00 (1.27–3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82–1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 μT had estimates compatible with no increased risk, while the 0.8% of children with exposures ≥ 0.4 μT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Prevalence of Alzheimer's disease and other dementias in an elderly urban population Relationship with age, sex, and education

We studied the prevalence of different types of dementia in an elderly population in Stockholm, Sweden, in relation to age, sex, and education. The study confirmed Alzheimers disease (AD) as the most frequent type of dementia and the positive association of dementias with age, even in the most advanced ages. In contrast to previously reported data, we found the same proportion of AD and vascular dementia in the different age strata, and no sex differences regarding the prevalence of different dementia types. Finally, less educated people had a higher prevalence of all dementias, due essentially to a higher prevalence of alcoholic dementia and unspecified type of dementia. The prevalence of AD was similar across different levels of education.

Fatty fish consumption and risk of prostate cancer

Consumption of fatty fish might reduce the risk of prostate cancer, although epidemiological studies of fish consumption are rare. We studied the association between fish consumption and prostate cancer in a population-based prospective cohort of 6272 Swedish men. During 30 years of follow-up, men who ate no fish had a two-fold to three-fold higher frequency of prostate cancer than those who ate moderate or high amounts did. Our results suggest that fish consumption could be associated with decreased risk of prostate cancer.

Epidemiology of health effects of radiofrequency exposure.

We have undertaken a comprehensive review of epidemiologic studies about the effects of radiofrequency fields (RFs) on human health in order to summarize the current state of knowledge, explain the methodologic issues that are involved, and aid in the planning of future studies. There have been a large number of occupational studies over several decades, particularly on cancer, cardiovascular disease, adverse reproductive outcome, and cataract, in relation to RF exposure. More recently, there have been studies of residential exposure, mainly from radio and television transmitters, and especially focusing on leukemia. There have also been studies of mobile telephone users, particularly on brain tumors and less often on other cancers and on symptoms. Results of these studies to date give no consistent or convincing evidence of a causal relation between RF exposure and any adverse health effect. On the other hand, the studies have too many deficiencies to rule out an association. A key concern across all studies is the quality of assessment of RF exposure. Despite the ubiquity of new technologies using RFs, little is known about population exposure from RF sources and even less about the relative importance of different sources. Other cautions are that mobile phone studies to date have been able to address only relatively short lag periods, that almost no data are available on the consequences of childhood exposure, and that published data largely concentrate on a small number of outcomes, especially brain tumor and leukemia.

Mobile phone use and the risk of acoustic neuroma.

Background: Radiofrequency exposure from mobile phones is concentrated to the tissue closest to the handset, which includes the auditory nerve. If this type of exposure increases tumor risk, acoustic neuroma would be a potential concern. Methods: In this population-based case-control study we identified all cases age 20 to 69 years diagnosed with acoustic neuroma during 1999 to 2002 in certain parts of Sweden. Controls were randomly selected from the study base, stratified on age, sex, and residential area. Detailed information about mobile phone use and other environmental exposures was collected from 148 (93%) cases and 604 (72%) controls. Results: The overall odds ratio for acoustic neuroma associated with regular mobile phone use was 1.0 (95% confidence interval = 0.6–1.5). Ten years after the start of mobile phone use the estimates relative risk increased to 1.9 (0.9–4.1); when restricting to tumors on the same side of the head as the phone was normally used, the relative risk was 3.9 (1.6–9.5). Conclusions: Our findings do not indicate an increased risk of acoustic neuroma related to short-term mobile phone use after a short latency period. However, our data suggest an increased risk of acoustic neuroma associated with mobile phone use of at least 10 years’ duration.

Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort

Objective To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. Design Population based cohort study with follow-up over 35 years. Setting Municipality of Uppsala, Sweden. Participants 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. Main outcome measure Total (all cause) mortality. Results The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). Conclusions Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

Mobile phone use and risk of acoustic neuroma: results of the Interphone case–control study in five North European countries

There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population-based case–control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR)=0.9, 95% confidence interval (CI): 0.7–1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR=1.8, 95% CI: 1.1–3.1). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out.

Role of medical history in brain tumour development. Results from the international adult brain tumour study

In an international population‐based case‐control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age‐ and gender‐matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40–12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti‐epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49–0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61–0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation. Int. J. Cancer82:155–160, 1999.