Risk of solid cancer in the offspring of female workers of the Mayak nuclear facility in the Southern Urals, Russian Federation.

Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases.

Incidence of cutaneous malignant melanoma in Denmark, 1978-2007.

BACKGROUND: Incidence rates of cutaneous malignant melanoma (CMM) have been increasing markedly worldwide. The ongoing debate about possible overdiagnosis remains unresolved. OBJECTIVES: To determine the population-based incidence of CMM in Denmark between 1978 and 2007 and to analyse sex-, site- and extent of disease-specific changes in incidence rates of CMM over time. METHODS: We used the virtually complete nationwide Danish Cancer Register in this population-based study, which contains data on 25,851 cases reported in Denmark between 1978 and 2007. We calculated age-standardized (world standard population) incidence rates per 100,000 person-years and age-specific rates. RESULTS: The age-standardized incidence rates increased from 6·5 to 14·4 among men and from 8·6 to 18·9 among women. During the last 5 years of the study period, a sudden marked increase was seen in women of all ages and in men aged 65 years or older. The most marked site-specific change was in the incidence of melanoma on the trunk in both men and women. An increase in the rates of disease with regional spread was seen during the last 10 years of observation. CONCLUSIONS: The incidence rate of CMM more than doubled in Denmark between 1978 and 2007. The increases in both site-specific incidence rates and CMM with regional spread suggest an association with risk behaviour, such as intermittent sun exposure, although possible overdiagnosis must be taken into account in evaluating the implications of the increase.

Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study.

OBJECTIVES: The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. METHODS: We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. RESULTS: The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. CONCLUSIONS: While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk of brain tumours from RF exposure from mobile phones.

Effect of Internet peer-support groups on psychosocial adjustment to cancer: a randomised study.

BACKGROUND: We conducted a randomised study to investigate whether providing a self-guided Internet support group to cancer patients affected mood disturbance and adjustment to cancer. METHODS: Baseline and 1-, 6- and 12-month assessments were conducted from 2004 to 2006 at a national rehabilitation centre in Denmark. A total of 58 rehabilitation course weeks including 921 survivors of various cancers were randomly assigned to a control or an intervention group by cluster randomisation. The intervention was a lecture on the use of the Internet for support and information followed by participation in an Internet support group. Outcome measures included self-reported mood disturbance, adjustment to cancer and self-rated health. Differences in scores were compared between the control group and the intervention group. RESULTS: The effect of the intervention on mood disturbance and adjustment to cancer showed a transient difference at the 6-month follow-up, where the intervention group reported less reduction in anxious preoccupation (P=0.04), helplessness (P=0.002), confusion (P=0.001) and depression (P=0.04). Otherwise no significant effects were observed. CONCLUSION: We conclude that use of Internet-based support groups in cancer patients still needs to confirm long-lasting psychological effects.

Can loud noise cause acoustic neuroma? Analysis of the INTERPHONE study in France.

OBJECTIVES: To investigate possible associations between risk of acoustic neuroma and exposure to loud noise in leisure and occupational settings. METHODS: A case-control study was conducted in France within the international INTERPHONE study. The cases were the 108 subjects diagnosed with acoustic neuroma between 1 June 2000 and 31 August 2003. Two controls per case were selected from the electoral rolls and individually matched for gender, age (5 years) and area (local authority district) of residence at the time of the case diagnosis. Multivariate analyses were conducted using conditional logistic regression. Adjustment was made for socioeconomic status. RESULTS: Acoustic neuroma was found to be associated with loud noise exposure (odds ratio (OR) = 2.55; 95% CI 1.35 to 4.82), both in leisure settings, particularly when listening to loud music (OR = 3.88; 95% CI 1.48 to 10.17) and at work (OR = 2.26; 95% CI 1.08 to 4.72). This risk increased with exposure duration (>6 years' leisure exposure: OR = 3.15; 95% CI 1.07 to 9.24). Risk varied according to the type of noise (continuous or explosive vs intermittent). CONCLUSION: The present results agree with other recent reports implicating loud noise in the risk of acoustic neuroma.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment.

OBJECTIVES: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. METHODS: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. RESULTS: Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. CONCLUSIONS: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.

Distribution of RF energy emitted by mobile phones in anatomical structures of the brain.

The rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in possible carcinogenic effects of radio frequency (RF). Because exposure to RF from phones is localized, if a risk exists it is likely to be greatest for tumours in regions with greatest energy absorption. The objective of the current paper was to characterize the spatial distribution of RF energy in the brain, using results of measurements made in two laboratories on 110 phones used in Europe or Japan. Most (97-99% depending on frequency) appears to be absorbed in the brain hemisphere on the side where the phone is used, mainly (50-60%) in the temporal lobe. The average relative SAR is highest in the temporal lobe (6-15%, depending on frequency, of the spatial peak SAR in the most exposed region of the brain) and the cerebellum (2-10%) and decreases very rapidly with increasing depth, particularly at higher frequencies. The SAR distribution appears to be fairly similar across phone models, between older and newer phones and between phones with different antenna types and positions. Analyses of risk by location of tumour are therefore important for the interpretation of results of studies of brain tumours in relation to mobile phone use.

[Cell Phones and Risk of brain and acoustic nerve tumours: the French INTERPHONE case-control study]. / Téléphone mobile, risque de tumeurs cérébrales et du nerf vestibuloacoustique: l'étude cas-témoins INTERPHONE en France.

BACKGROUND: Use of cell phones has increased dramatically since 1992 when they were first introduced in France. Certain electromagnetic fields (at extremely low frequency) have been recognized as possibly carcinogenic by the International Agency for Research on Cancer. Given the use of radiofrequency technology in cell phones, the rapid increase in the number of cell phones has generated concerns about the existence of a potential health hazard. To evaluate the relationship between the use of cell phones and the development of tumors of the head, a multicentric international study (INTERPHONE), coordinated by the International Agency for Research on Cancer, was carried out in 13 countries. This publication reports the results of the French part of the INTERPHONE study. METHODS: INTERPHONE is a case-control study focused on tumors of the brain and central nervous system: gliomas, meningiomas and neuromas of cranial nerves. Eligible cases were men and women, residents of Paris or Lyon, aged 30-59, newly diagnosed with a first primary tumor between February 2001 and August 2003. The diagnoses were all either histologically confirmed or based upon unequivocal radiological images. Controls were matched for gender, age (+/-5 years) and place of residence. They were randomly drawn from electoral rolls. Detailed information was collected for all subjects during a computer-assisted face-to-face interview. Conditional logistic regression was used to estimate the odds ratio (OR) for an association between the use of cell phones and risk of each type of cancer. RESULTS: Regular cell phone use was not associated with an increased risk of neuroma (OR=0,92; 95% confidence interval=[0.53-1.59]), meningioma (OR=0,74; 95% confidence interval=[0.43-1.28]) or glioma (OR=1.15; 95% confidence interval=[0.65-2.05]). Although these results are not statistically significant, a general tendency was observed for an increased risk of glioma among the heaviest users: long-term users, heavy users, users with the largest numbers of telephones. CONCLUSION: No significant increased risk for glioma, meningioma or neuroma was observed among cell phone users participating in Interphone. The statistical power of the study is limited, however. Our results, suggesting the possibility of an increased risk among the heaviest users, therefore need to be verified in the international INTERPHONE analyses.

Cancer Incidence after In Utero Exposure to Ionizing Radiation in Techa River Residents.

Health effects of in utero exposure to ionizing radiation, especially among adults, are still unclear. The aim of this study was to analyze cancer risk in a cohort of subjects exposed in utero due to releases of nuclear waste into the Techa River in the Southern Urals, taking into account additional postnatal exposure. Analysis for solid cancer was based on 242 cases among 10,482 cohort members, accumulating 381,948 person-years at risk, with follow-up from 1956-2009, while analysis for hematological malignancies was based on 26 cases among 11,070 persons, with 423,502 person-years at risk, with follow-up from 1953-2009. Mean doses accumulated in soft tissues and in red bone marrow during the prenatal period were 4 mGy and 30 mGy, respectively. Additional respective mean postnatal doses received by cohort members were 11 and 84 mGy. Poisson regression analysis was used to estimate the excess relative risk (ERR) of cancer incidence related to in utero and postnatal doses. No association was observed for in utero exposure with solid cancer risk [ERR per 10 mGy: -0.007; 95% confidence interval (CI): <-0.107; 0.148] or with hematological malignancy risk (ERR/10 mGy: -0.011; 95% CI: <-0.015; 0.099). However, ERR of solid cancer increased significantly with increasing postnatal dose (ERR/10 mGy: 0.11; 95% CI: 0.04; 0.22). The very wide confidence intervals in these ERR results are similar to those of studies performed on the LSS cohort and the offspring of the Mayak Female Worker Cohort, as well as case-control studies of effects after in utero medical exposure. There were limitations of this study, with decreased statistical power, due to the low prenatal doses received by most of the cohort members, the small number of cancer cases and the absence of cohort members over the age of 59 years (living cohort members had reached 49-59 years of age). Further aging of the cohort and extension of the follow-up period will enhance the statistical power of this study in the future. There is a shortage of cohort studies reporting on the effects of prenatal radiation exposure, as well as information on chronic exposure during the prenatal period. Therefore, further research of this unique cohort will be a useful addition to the published literature on this subject, and a valuable means of elucidating the long-term effects of low-dose radiation exposure in the fetus.

Validation of short term recall of mobile phone use for the Interphone study.

AIM: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. METHODS: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. RESULTS: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. CONCLUSIONS: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Risk of Hematologic Malignancies in the Offspring of Female Workers of the Mayak Nuclear Facility in the Southern Urals, Russian Federation.

Long-term effects of in utero exposure to ionizing radiation remain poorly quantified in humans. In this study, the risk of hematologic malignancies was investigated in offspring of female workers of the Mayak Production Association, a large Russian nuclear facility. Excess relative risks (ERR) for exposure to gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who were born between January 1, 1948 and December 31, 1988 and followed until 2009. An unstable linear ERR of 1.12 (95% CI 0.11-3.44) per 100 mGy gamma exposure in utero was estimated based on 32 incident hematologic malignancies in 277,002 person-years under risk. The ERR was increased in the dose category 20-79 mGy gamma exposure in utero (1.75, 95% CI 0.04; 5.63), while the other dose categories showed decreased or unstable estimates. Leukemia showed an ERR of 1.76 (95% CI 0.01-8.33) per 100 mGy based on 13 cases. There was no consistent association with plutonium exposure. While an increased risk of hematologic malignancies after gamma exposure in utero was suggested, the small numbers prevented more definitive conclusions.

Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters.

Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated to be 1.93x10(-2) Sv(-1) (95% CI 1.14, 3.38), or 0.44 years of life lost Sv(-1) (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36x10(-2) Sv(-1) (95% CI 8.41, 12.42), or 1.38 years of life lost Sv(-1) (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods; however, leukaemia risks were somewhat higher, by 10-35%, than those predicted by classical likelihood-based methods. This is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk.

Stochastic algorithms for Markov models estimation with intermittent missing data.

Multistate Markov models are frequently used to characterize disease processes, but their estimation from longitudinal data is often hampered by complex patterns of incompleteness. Two algorithms for estimating Markov chain models in the case of intermittent missing data in longitudinal studies, a stochastic EM algorithm and the Gibbs sampler, are described. The first can be viewed as a random perturbation of the EM algorithm and is appropriate when the M step is straightforward but the E step is computationally burdensome. It leads to a good approximation of the maximum likelihood estimates. The Gibbs sampler is used for a full Bayesian inference. The performances of the two algorithms are illustrated on two simulated data sets. A motivating example concerned with the modelling of the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of 105 young children in Cameroon is described and briefly analyzed.