Effects of Recall and Selection Biases on Modeling Cancer Risk From Mobile Phone Use: Results From a Case-Control Simulation Study.

BACKGROUND: The largest case-control study (Interphone study) investigating glioma risk related to mobile phone use showed a J-shaped relationship with reduced relative risks for moderate use and a 40% increased relative risk among the 10% heaviest regular mobile phone users, using a categorical risk model based on deciles of lifetime duration of use among ever regular users. METHODS: We conducted Monte Carlo simulations examining whether the reported estimates are compatible with an assumption of no effect of mobile phone use on glioma risk when the various forms of biases present in the Interphone study are accounted for. Four scenarios of sources of error in self-reported mobile phone use were considered, along with selection bias. Input parameters used for simulations were those obtained from Interphone validation studies on reporting accuracy and from using a nonresponse questionnaire. RESULTS: We found that the scenario simultaneously modeling systematic and random reporting errors produced a J-shaped relationship perfectly compatible with the observed relationship from the main Interphone study with a simulated spurious increased relative risk among heaviest users (odds ratio = 1.91) compared with never regular users. The main determinant for producing this J shape was higher reporting error variance in cases compared with controls, as observed in the validation studies. Selection bias contributed to the reduced risks as well. CONCLUSIONS: Some uncertainty remains, but the evidence from the present simulation study shifts the overall assessment to making it less likely that heavy mobile phone use is causally related to an increased glioma risk.

Association of allergic diseases and epilepsy with risk of glioma, meningioma and acoustic neuroma: results from the INTERPHONE international case-control study.

We investigated the association of allergic diseases and epilepsy with risk of brain tumours, in Interphone, a 13-country case-control study. Data were obtained from 2693 glioma cases, 2396 meningioma cases, and 1102 acoustic neuroma cases and their 6321 controls. Conditional logistic regression models were used to estimate pooled odds ratios (ORs) and their respective 95% confidence intervals (CIs), adjusted for education and time at interview. Reduced ORs were observed for glioma in relation to physician-diagnosed asthma (OR = 0.73; CI 0.58-0.92), hay fever (OR 0.72; CI 0.61-0.86), and eczema (OR 0.78, CI 0.64-0.94), but not for meningioma or acoustic neuroma. Previous diagnosis of epilepsy was associated with an increased OR for glioma (2.94; CI 1.87-4.63) and for meningioma (2.12; CI 1.27-3.56), but not for acoustic neuroma. This large-scale case-control study adds to the growing evidence that people with allergies have a lower risk of developing glioma, but not meningioma or acoustic neuroma. It also supports clinical observations of epilepsy prior to the diagnosis of glioma and meningioma.

Brain and Salivary Gland Tumors and Mobile Phone Use: Evaluating the Evidence from Various Epidemiological Study Designs.

Mobile phones (MPs) are the most relevant source of radiofrequency electromagnetic field (RF-EMF) exposure to the brain and the salivary gland. Whether this exposure implies a cancer risk has been addressed in several case-control and few cohort studies. A meta-analysis of these studies does not show increased risks for meningioma, pituitary, and salivary gland tumors. For glioma and acoustic neuroma, the results are heterogeneous, with few case-control studies reporting substantially increased risks. However, these elevated risks are not coherent with observed incidence time trends, which are considered informative for this specific topic owing to the steep increase in MP use, the availability of virtually complete cancer registry data from many countries, and the limited number of known competing environmental risk factors. In conclusion, epidemiological studies do not suggest increased brain or salivary gland tumor risk with MP use, although some uncertainty remains regarding long latency periods (>15 years), rare brain tumor subtypes, and MP usage during childhood.

The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study.

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use.

Mortality from cancer and other causes in commercial airline crews: a joint analysis of cohorts from 10 countries.

BACKGROUND: Commercial airline crew is one of the occupational groups with the highest exposures to ionising radiation. Crew members are also exposed to other physical risk factors and subject to potential disruption of circadian rhythms. METHODS: This study analyses mortality in a pooled cohort of 93 771 crew members from 10 countries. The cohort was followed for a mean of 21.7 years (2.0 million person-years), during which 5508 deaths occurred. RESULTS: The overall mortality was strongly reduced in male cockpit (SMR 0.56) and female cabin crews (SMR 0.73). The mortality from radiation-related cancers was also reduced in male cockpit crew (SMR 0.73), but not in female or male cabin crews (SMR 1.01 and 1.00, respectively). The mortality from female breast cancer (SMR 1.06), leukaemia and brain cancer was similar to that of the general population. The mortality from malignant melanoma was elevated, and significantly so in male cockpit crew (SMR 1.57). The mortality from cardiovascular diseases was strongly reduced (SMR 0.46). On the other hand, the mortality from aircraft accidents was exceedingly high (SMR 33.9), as was that from AIDS in male cabin crew (SMR 14.0). CONCLUSIONS: This large study with highly complete follow-up shows a reduced overall mortality in male cockpit and female cabin crews, an increased mortality of aircraft accidents and an increased mortality in malignant skin melanoma in cockpit crew. Further analysis after longer follow-up is recommended.

Mobile phone use and risk of intracranial tumors: a consistency analysis.

A meta-analysis of studies on intracranial tumors and mobile phone use published by the end of 2012 was performed to evaluate the overall consistency of findings, assess the sensitivity of results to changes in the dataset, and try to detect the sources of between-study heterogeneity. Twenty-nine papers met our inclusion criteria. These papers reported on 47 eligible studies (17 on glioma, 15 on meningioma, 15 on acoustic neuroma), consisting of either primary investigations or pooled analyses. Five combinations of non-overlapping studies per outcome were identified. The combined relative risks (cRRs) in long-term mobile phone users (≥10 years) ranged between 0.98 (0.75-1.28) and 1.11 (0.86-1.44) for meningioma, with little heterogeneity across studies. High heterogeneity was detected across estimates of glioma and acoustic neuroma risk in long term users, with cRRs ranging between 1.19 (95% CI 0.86-1.64) and 1.40 (0.96-2.04), and from 1.14 (0.65-1.99) to 1.33 (0.65-2.73), respectively. A meta-regression of primary studies showed that the methodological differences embedded in the variable "study-group" explained most of the overall heterogeneity in results. Summary risk estimates based on heterogeneous findings should not be over-interpreted. Overall, the results of our study detract from the hypothesis that mobile phone use affects the occurrence of intracranial tumors. However, reproducibility (or lack of) is just one clue in the critical appraisal of epidemiological evidence. Based on other considerations, such as the limited knowledge currently available on risk beyond 15 years from first exposure, or following mobile phone use started in childhood, the pursuance of epidemiological surveillance is warranted.

Risk of childhood leukaemia and non-Hodgkin's lymphoma after parental occupational exposure to solvents and other agents: the SETIL Study.

AIM: In the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures. METHODS: All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0-10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure. RESULTS: 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified. Increased risk of childhood leukaemia was found for maternal exposure to aliphatic (OR 4.3) or aromatic hydrocarbons (OR 3.8) in the preconception period, and for paternal exposure to diesel exhaust (OR 1.4), lead exposure (OR 1.7) and mineral oils (OR 1.4)[corrected]. Risk of NHL appeared to be related to paternal exposure to oxygenated solvents (OR 2.5) and petrol exhaust (OR 2.2). CONCLUSIONS: We found increased risk for childhood leukaemia associated with maternal occupational exposure to aromatic and aliphatic hydrocarbons, particularly in the preconception period; increased risks were also observed for paternal exposure to diesel exhaust fumes, mineral oils and lead. The risk of NHL appeared to be related to paternal exposure to oxygenated solvent and petrol exhausts.

NextGEM: Next-Generation Integrated Sensing and Analytical System for Monitoring and Assessing Radiofrequency Electromagnetic Field Exposure and Health.

The evolution of emerging technologies that use Radio Frequency Electromagnetic Field (RF-EMF) has increased the interest of the scientific community and society regarding the possible adverse effects on human health and the environment. This article provides NextGEM's vision to assure safety for EU citizens when employing existing and future EMF-based telecommunication technologies. This is accomplished by generating relevant knowledge that ascertains appropriate prevention and control/actuation actions regarding RF-EMF exposure in residential, public, and occupational settings. Fulfilling this vision, NextGEM commits to the need for a healthy living and working environment under safe RF-EMF exposure conditions that can be trusted by people and be in line with the regulations and laws developed by public authorities. NextGEM provides a framework for generating health-relevant scientific knowledge and data on new scenarios of exposure to RF-EMF in multiple frequency bands and developing and validating tools for evidence-based risk assessment. Finally, NextGEM's Innovation and Knowledge Hub (NIKH) will offer a standardized way for European regulatory authorities and the scientific community to store and assess project outcomes and provide access to findable, accessible, interoperable, and reusable (FAIR) data.

Survival of European patients with central nervous system tumors.

We present estimates of population-based 5-year relative survival for adult Europeans diagnosed with central nervous system tumors, by morphology (14 categories based on cell lineage and malignancy grade), sex, age at diagnosis and region (UK and Ireland, Northern, Central, Eastern and Southern Europe) for the most recent period with available data (2000-2002). Sources were 39 EUROCARE cancer registries with continuous data from 1996 to 2002. Survival time trends (1988 to 2002) were estimated from 24 cancer registries with continuous data from 1988. Overall 5-year relative survival was 85.0% for benign, 19.9% for malignant tumors. Benign tumor survival ranged from 90.6% (Northern Europe) to 77.4% (UK and Ireland); for malignant tumors the range was 25.1% (Northern Europe) to 15.6% (UK and Ireland). Survival decreased with age at diagnosis and was slightly better for women (malignant tumors only). For glial tumors, survival varied from 83.5% (ependymoma and choroid plexus) to 2.7% (glioblastoma); and for non-glioma tumors from 96.5% (neurinoma) to 44.9% (primitive neuroectoderm tumor/medulloblastoma). Survival differences between regions narrowed after adjustment for morphology and age, and were mainly attributable to differences in morphology mix; however UK and Ireland and Eastern Europe patients still had 40% and 30% higher excess risk of death, respectively, than Northern Europe patients (reference). Survival for benign tumors increased from 69.3% (1988-1990) to 77.1% (2000-2002); but survival for malignant tumors did not improve indicating no useful advances in treatment over the 14-year study period, notwithstanding major improvement in the diagnosis and treatment of other solid cancers.

Diagnostic radiological examinations and risk of intracranial tumours in adults-findings from the Interphone Study.

BACKGROUND: Exposure to high doses of ionizing radiation is among the few well-established brain tumour risk factors. We used data from the Interphone study to evaluate the effects of exposure to low-dose radiation from diagnostic radiological examinations on glioma, meningioma and acoustic neuroma risk. METHODS: Brain tumour cases (2644 gliomas, 2236 meningiomas, 1083 neuromas) diagnosed in 2000-02 were identified through hospitals in 13 countries, and 6068 controls (population-based controls in most centres) were included in the analysis. Participation across all centres was 64% for glioma cases, 78% for meningioma cases, 82% for acoustic neuroma cases and 53% for controls. Information on previous diagnostic radiological examinations was obtained by interviews, including the frequency, timing and indication for the examinations. Typical brain doses per type of examination were estimated based on the literature. Examinations within the 5 years before the index date were excluded from the dose estimation. Adjusted odds ratios were estimated using conditional logistic regression. RESULTS: No materially or consistently increased odds ratios for glioma, meningioma or acoustic neuroma were found for any specific type of examination, including computed tomography of the head and cerebral angiography. The only indication of an elevated risk was an increasing trend in risk of meningioma with the number of isotope scans, but no such trends for other examinations were observed. No gradient was found in risk with estimated brain dose. Age at exposure did not substantially modify the findings. Sensitivity analyses gave results consistent with the main analysis. CONCLUSIONS: There was no consistent evidence for increased risks of brain tumours with X-ray examinations, although error from selection and recall bias cannot be completely excluded. A cautious interpretation is warranted for the observed association between isotope scans and meningioma.

Location of gliomas in relation to mobile telephone use: a case-case and case-specular analysis.

The energy absorbed from the radio-frequency fields of mobile telephones depends strongly on distance from the source. The authors' objective in this study was to evaluate whether gliomas occur preferentially in the areas of the brain having the highest radio-frequency exposure. The authors used 2 approaches: In a case-case analysis, tumor locations were compared with varying exposure levels; in a case-specular analysis, a hypothetical reference location was assigned for each glioma, and the distances from the actual and specular locations to the handset were compared. The study included 888 gliomas from 7 European countries (2000-2004), with tumor midpoints defined on a 3-dimensional grid based on radiologic images. The case-case analyses were carried out using unconditional logistic regression, whereas in the case-specular analysis, conditional logistic regression was used. In the case-case analyses, tumors were located closest to the source of exposure among never-regular and contralateral users, but not statistically significantly. In the case-specular analysis, the mean distances between exposure source and location were similar for cases and speculars. These results do not suggest that gliomas in mobile phone users are preferentially located in the parts of the brain with the highest radio-frequency fields from mobile phones.

["An Italian Court recognizes the occupational origin of a trigeminal neuroma in a mobile telephone user: a case-study of the complex relationships between science and laws"]. / Una Corte italiana riconosce l'origine professionale di un neurinoma del trigemino in un utilizzatore di telefoni mobili: un esempio concreto dei complessi rapporti tra scienza e diritto.

BACKGROUND: Scientific knowledge is essential for the resolution of disputes in law and administrative applications (such as toxic tort litigation and workers' compensation) and provides essential input for public policy decisions. There are no socially agreed-upon rules for the application of this knowledge except in the law. On a practical level, the legal system lacks the ability to assess the validity of scientific knowledge that can be used as evidence and therefore relies heavily on expert opinion. A key issue is how to ensure that professionals in any field provide judges with sound advice, based on relevant and reliable scientific evidence. The search for solutions to this problem seems particularly urgent in Italy, a country where a number of unprecedented verdicts of guilt have been pronounced in trials involving personal injuries from exposure to electromagnetic fields. OBJECTIVES AND METHODS: An Italian Court has recently recognized the occupational origin of a trigeminal neuroma in a mobile telephone user, and ordered the Italian Workers' Compensation Authority (INAIL) to award the applicant compensation for a high degree (80%) of permanent disability. We describe and discuss the salient aspects of this sentence as a case-study in the framework of the use (and misuse) of scientific evidence in toxic-tort litigations. RESULTS: Based on the motivations of the verdict, it appears that the judge relied on seriously flawed expert testimonies. The "experts" who served in this particular trial were clearly inexperienced in forensic epidemiology in general, as well as in the topic at hand. Selective overviews of scientific evidence concerning cancer risks from mobile phone use were provided, along with misleading interpretations of findings from relevant epidemiologic studies (including the dismissal of the Interphone study results on the grounds of purported bias resulting from industry funding). The necessary requirements to proceed to causal inferences at individual level were not taken into account and inappropriate methods to derive estimates of personal risk were used. CONCLUSIONS: A comprehensive strategy to improve the quality of expert witness testimonies in legal proceedings and promote just and equitable verdicts is urgently needed in Italy. Contrary to other countries, such as the United States or the United Kingdom, legal standards for expert testimony, such as preliminary assessment of scientific evidence admissibility and qualification requirements for professionals acting as experts in the courtroom, are lacking in our country. In this and similar contexts, recommendations issued by professional associations (including EBEA and BEMS) could play a role of paramount importance. As examples, we refer to the guidelines recently endorsed by the UK General Medical Council and the American Academy of Pediatrics.

Genotoxicity of radiofrequency electromagnetic fields: Protocol for a systematic review of in vitro studies.

BACKGROUND: Exposure to radiofrequency electromagnetic fields (RF-EMF, 100 kHz - 300 GHz) emitted by wireless communication technologies is pervasive and ubiquitous. Concern has been raised about possible adverse effects to human health. In 2011 the International Agency for Research on Cancer has classified RF-EMF as possibly carcinogenic to humans, highlighting that the evidence is weak and far from conclusive. Updated systematic reviews of the scientific literature on this topic are lacking, especially for mechanistic studies. OBJECTIVES: To develop a protocol for a systematic review of experimental studies investigating genotoxic effects induced by RF-EMF in in vitro cellular models. Genotoxicity is one of the key-biological indicators of carcinogenicity, and the most common characteristics of established carcinogens. The predefined procedures for conducting the systematic review are outlined below. METHODS: We will follow the guidelines developed by the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT), adapted to the evaluation of in vitro studies. ELIGIBILITY CRITERIA: We will include experimental in vitro studies addressing the relationship between controlled exposures to RF-EMF and genotoxicity in mammalian cells only. Eligibility for inclusion will be further restricted to peer reviewed articles reporting findings from primary studies. INFORMATION SOURCES: We will search the scientific literature databases NCBI PubMed, Web of Science, and EMF-Portal. No filter on publication date will be applied. Only studies published in English will be considered. The reference lists of the included papers and available reviews will be screened for unidentified relevant papers. References will be managed through Endnote X9 software. DATA EXTRACTION AND SYNTHESIS OF RESULTS: Data from included papers will be extracted according to predefined forms. Heterogeneity within the available evidence will determine the type of evidence synthesis that is appropriate. Findings will be summarized in tables, graphical displays and in a narrative synthesis of the available evidences. A meta-analysis will be carried out if subgroups of studies homogeneous in terms of exposure characteristics, endpoint, and cell types will be identified. RISK OF BIAS: The internal validity of included studies will be assessed using the NTP-OHAT Risk of Bias Rating Tool for animal studies, adapted to in vitro studies. This stage of the process will be managed through the Health Assessment Workspace Collaborative (HAWC). EVIDENCE APPRAISAL: To rate confidence in the body of evidence, we will use the OHAT GRADE-based approach for animal studies. FRAMEWORK AND FUNDING: This protocol concerns one of the evidence streams considered in a larger systematic review of the scientific literature on the potential carcinogenicity of RF-EMF, performed by scientists from several Italian public research agencies. The project is supported by the Italian Workers' Compensation Authority (INAIL) in the framework of the CRA with the Istituto Superiore di Sanità "BRiC 2018/06 - Scientific evidence on the carcinogenicity of radiofrequency electromagnetic fields".

The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A protocol for a systematic review of human observational studies.

BACKGROUND: The World Health Organization (WHO) has an ongoing project to assess potential health effects of exposure to radiofrequency electromagnetic fields (RF-EMF) in the general and working population. Here we present the protocol for a systematic review of the scientific literature on cancer hazards from exposure to RF-EMF in humans, commissioned by the WHO as part of that project. OBJECTIVE: To assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to RF-EMF and risk of neoplastic diseases. ELIGIBILITY CRITERIA: We will include cohort and case-control studies investigating neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of handheld transceivers or RF-emitting equipment in the workplace (SR-C). While no restriction on tumour type will be applied, we will focus on selected neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). INFORMATION SOURCES: Eligible studies will be identified through Medline, Embase, and EMF-Portal. RISK-OF-BIAS ASSESSMENT: We will use a tailored version of the OHAT's tool to evaluate the study's internal validity. DATA SYNTHESIS: We will consider separately studies on different tumours, neoplasm-specific risks from different exposure sources, and a given exposure-outcome pair in adults and children. When a quantitative synthesis of findings can be envisaged, the main aims of the meta-analysis will be to assess the strength of association and the shape of the exposure-response relationship; to quantify the degree of heterogeneity across studies; and explore the sources of inconsistency (if any). When a meta-analysis is judged inappropriate, we will perform a narrative synthesis, complemented by a structured tabulation of results and appropriate visual displays. EVIDENCE ASSESSMENT: Confidence in evidence will be assessed in line with the GRADE approach. FUNDING: This project is supported by the World Health Organization. Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; ARPANSA as a WHO Collaborating Centre for Radiation Protection. REGISTRATION: PROSPERO CRD42021236798.

Electromagnetic fields and epidemiology: an overview inspired by the fourth course at the International School of Bioelectromagnetics.

The fourth course at the International School of Bioelectromagnetics addressed various aspects of the epidemiology of exposure to electromagnetic fields (EMF). In this overview, inspired by the lectures and the discussions among participants, we summarize current knowledge on exposure to EMF and disease risk, with emphasis on studies of use of mobile phones and brain tumours and exposure to power lines and childhood leukaemia. Sources of bias and error hamper straightforward conclusions in some areas and, in order to move forward, improvements in study design and exposure assessment are necessary. The scientific evidence available to date on possible long-term effects from exposure to ELF and RF fields is not strong enough to revise current protection limits based on the known acute effects of such exposures. Precautionary measures may be considered to reduce ELF exposure of children or exposure to RF during mobile phone use, keeping in mind that it is unclear whether they involve any preventive benefit. Possible health effects from mobile phone use in adults and in children should be investigated further by prospective epidemiological studies with improved exposure assessment and brain tumour incidence rates should be monitored. Further studies on the relation between childhood leukaemia and ELF magnetic fields would be worthwhile if they focus on heavily exposed groups and attempt to minimize possible selection bias. In conclusion, epidemiological studies conducted with appropriate diligence can play a key role in finding the answers.

Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study.

Objective Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000-2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. Methods Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. Results The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4-1.9). OR were 1.5 (95% CI 1.3-1.9) for only occupational noise, 1.9 (95% CI 1.4-2.6) for only leisure noise and 1.7 (95% CI 1.2-2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. Conclusion The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.

[Review of epidemiological studies of cancer risk among Gulf War and Balkans veterans]. / Rassegna degli studi epidemiologici sul rischio di tumori tra i militari della Guerra del Golfo e delle missioni nei Balcani.

OBJECTIVE: Analysis of the available epidemiological evidence on cancer risk among Gulf war and Balkans veterans. DESIGN AND SETTING: Eligible for the review were all studies published in peer-reviewed journals indexed in MedLine by the end of 2007. The review includes twelve studies published between 1996 and 2006 All of them are retrospective cohort studies focused on different outcomes: mortality, hospitalizations or cancer incidence. The study populations are from US, UK, Sweden, Denmark and Italy. The description ofthe studies reviewed focusses on their main features (design, study population, health outcomes and ascertainment procedures, analytical methods). RESULTS: Results are summarized by cancer site: all cancers, neoplasms that may be a target of exposure to depleted uranium (lung cancer, leukemias, kidney cancer, bone cancer), and other neoplasms (lymphomas, brain cancer, and cancer of the testis) relatively frequent among young adults. The overall incidence of cancers is not increased in the cohort studies of Gulf war and Balkans veterans published to date, nor there is consistent evidence of excess risks of neoplasms possibly related to exposure to depleted uranium. However, in the Danish cohort of Balkans veterans an increased risk ofbone cancer has been observed, but the excess disappeared when a 1-year latency was considered. An increased brain cancer risk in relation to exposure to nerve-gas agents has been observed. Sporadic excesses of Hodgkin lymphoma and testicular cancer in deployed veterans have been reported. CONCLUSION: None of the studies reviewed could obiectively assess exposures to depleted uranium or to other potentially carcinogenic agents experienced in the theaters. The study cohorts are young and the follow-up periods are probably too short to capture excesses of long latency outcomes. The update of the follow-up of the cohorts and studies of other cohorts with a better assessment of exposure to depleted uranium and to other potentially relevant risk factors are warranted.

Air pollution and lung function among susceptible adult subjects: a panel study.

BACKGROUND: Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. METHODS: Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM10-2.5) and fine (PM2.5) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and sulphur dioxide (SO2) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. RESULTS: Decrements in lung function indices (FVC and/or FEV1) associated with increasing concentrations of PM2.5, NO2 and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO2 was associated with a decrease in FEV1. No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. CONCLUSION: This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function of the relatively young and mild asthmatics included in this study seems to worsen when ambient levels of NO2 increase.