Risk Factors For Brain Tumors Research Articles

Risk factors for childhood and adult primary brain tumors.

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumors in children. These tumors are very heterogeneous and can be broadly classified into malignant and benign (or non-malignant), and specific histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently under way for other histologic subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes. Key Point 1. Brain tumors are a heterogeneous group of tumors that vary significantly in incidence by age, sex, and race/ethnicity.2. The only well-validated risk factors for brain tumors are ionizing radiation (which increases risk in adults and children) and history of allergies (which decreases risk).3. Genome-wide association studies have identified 32 histology-specific inherited genetic variants associated with increased risk of these tumors.

Fluoroscopic Cranial Radiation Exposure in Spine Surgery: A Prospective Single-Center Evaluation in Operating Room Personnel.

Cranial radiation exposure during instrumented spine surgery is not well documented. We set out to measure this risk to the patient, surgeon, surgical resident, and scrub technician during these procedures. Forty-seven individuals were enrolled during a 1.5-year period between October 2014 and March 2016 at the University of New Mexico Department of Neurosurgery. Radiation doses were obtained through electronic dosimeters placed on the surgical cap over the temporal scalp (bilaterally on surgeon and resident assist, unilaterally on surgical scrub on the side facing radiation source) and on the midline of the patient's exposed cranium. Of the 47 procedures, 39 (83%) were open and 8 (17%) were minimally invasive or percutaneous instrumented procedures. A total of 91 motion segments were treated, with a mean of 1.9 levels per case (57% lumbosacral, 34% cervical, and 2.1% thoracic). Total fluoroscopic time was 12.9 minutes. Mean dose per case (mrem/case) was calculated for the spine surgeon (1.4), resident assist (1.4), surgical scrub (1.2), and the patient (3.6). All doses were within federal safety guidelines. A spine surgeon would need to perform more than 1400 cases per year to reach the current federal maximum permissible dose for head exposure. There was no difference in cranial radiation exposure between operating room staff during spine surgeries. Moreover, the doses measured at the cranium were within national safety limits. Current protective technologies have significantly reduced the amount of ionizing radiation exposure during routine spine procedures; however, changes in behavior or equipment may further reduce radiation exposure to health care workers. Radiation exposure to patients and hospital staff remains a major concern in the practice of modern spine surgery. Cranial exposure remains the only established environmental risk factor for brain tumors, such as gliomas and meningiomas. Our study shows that all those exposed to radiation during spine surgery had cranial doses well within the national safety limits.

Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors.

Gliomas are a group of primary brain tumors, the most common and aggressive subtype of which is glioblastoma. Glioblastoma has a median survival of just 15 months after diagnosis. Only previous exposure to ionizing radiation and particular inherited genetic syndromes are accepted risk factors for glioma; the vast majority of cases are thought to occur spontaneously. Previous observational studies have described associations between several risk factors and glioma, but studies are often conflicting and whether these associations reflect true casual relationships is unclear because observational studies may be susceptible to confounding, measurement error and reverse causation. Mendelian randomization (MR) is a form of instrumental variable analysis that can be used to provide supporting evidence for causal relationships between exposures (e.g., risk factors) and outcomes (e.g., disease onset). MR utilizes genetic variants, such as single nucleotide polymorphisms (SNPs), that are robustly associated with an exposure to determine whether there is a causal effect of the exposure on the outcome. MR is less susceptible to confounding, reverse causation and measurement errors as it is based on the random inheritance during conception of genetic variants that can be relatively accurately measured. In previous studies, MR has implicated a genetically predicted increase in telomere length with an increased risk of glioma, and found little evidence that obesity related factors, vitamin D or atopy are causal in glioma risk. In this review, we describe MR and its potential use to discover and validate novel risk factors, mechanistic factors, and therapeutic targets in glioma.

Genetic epidemiology and risk factors for brain tumors.

This report summarized current knowledge and findings relevant to environmental and genetic risk factors in brain tumors, with a particular focus on glioma. To date, the established risk factors for brain tumors are family history and ionizing radiation exposure; whereas there is an inverse association between tumors and other factors such as history of allergies, atopic conditions, chickenpox, and varicella zoster virus infection. To identify inherited genetic variants impacting susceptibility of brain tumors, large scale familial linkage-scan pedigree analysis, population-based candidate genes, and genome-wide association study were performed. More recently, next generation exome and whole genome sequencing studies were also conducted.

Brain tumor and environmental risk factors in young people- A literature review

Introduction: Despite brain tumors being one of the most frequent tumor type in young people, little is known on their etiological factors. The main objective was to review the scientific literature on the association between exposure to environmental risk factors and brain tumors in young people. Methods: The PUBMED database was searched to identify publications on environmental risk factors (ionizing and non-ionizing radiation, heavy metals, water quality, farming, air pollution, and environmental tobacco smoke) and brain cancer in young people. Results: A total of thirty one publications were identified. Ionizing radiation was the best established environmental risk factor. We found two studies showing an increased risk, four studies showing no association and seven suggesting an increased risk between brain cancer and ionizing radiation. With respect to heavy metals, we identified one study on cadmium which found an increased risk. On water quality, two studies suggested a possible association and another one observed no increased risk, except in women who drank exclusively well water during pregnancy. Six reports showed an increased risk related to farm residence, especially when handling pesticides, while another one found an inverse association. With respect to air pollution, the four articles that we found showed an increased risk. For environmental tobacco smoke, we found one study that reported an increased risk while two other studies found no significant association. Conclusions: Ionizing radiation is the most established environmental risk factor for brain tumors. Results for other environmental risk factors are inconclusive. More studies are needed to assess the association between environmental risk factors and brain tumors in young adults.

Epidemiology and diagnosis of brain tumors.

Brain tumors consist of a collection of neoplasms arising from within the brain or from systemic tumors that have metastasized to the brain. This article focuses on the most recent findings with regard to epidemiology, clinical presentation, neuroimaging evaluation, and diagnosis of brain tumors. Patients with brain tumors may present for care with a variety of signs and symptoms. The most frequent clinical presentations include seizure, headache, fatigue, and cognitive dysfunction. Currently, diagnosis and treatment response is largely evaluated by using MRI. However, molecular imaging may ultimately be better suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered in treatment. Contemporary neuropathology continues to play a key role in the multidisciplinary management of patients with brain tumors. Genetic and environmental risk factors for brain tumors remain largely unclear. Brain tumors represent a diverse spectrum of highly morbid cancers arising from different cells both from within the brain and from systemic tumors that have metastasized to the brain. The clinical manifestations of intracranial tumors are usually referable to the anatomic area of the brain involved or adjacent structures. The initial diagnosis of intracranial tumors is most efficiently made by imaging, generally MRI, although other techniques are being explored. The clinical manifestations, neuroimaging evaluation, and diagnosis of brain tumors are varied and dependent on the specific manner in which a patient presents for care. To date, specific causes of brain tumors remain elusive.

Perinatal and familial risk factors for brain tumors in childhood through young adulthood.

Perinatal factors, including high birth weight, have been associated with childhood brain tumors in case-control studies. However, the specific contributions of gestational age and fetal growth remain unknown, and these issues have never been examined in large cohort studies with follow-up into adulthood. We conducted a national cohort study of 3,571,574 persons born in Sweden in 1973-2008, followed up for brain tumor incidence through 2010 (maximum age 38 years) to examine perinatal and familial risk factors. There were 2,809 brain tumors in 69.7 million person-years of follow-up. After adjusting for potential confounders, significant risk factors for brain tumors included high fetal growth [incidence rate ratio (IRR) per additional 1 SD, 1.04; 95% confidence interval (CI), 1.01-1.08, P = 0.02], first-degree family history of a brain tumor (IRR, 2.43; 95% CI, 1.86-3.18, P < 0.001), parental country of birth (IRR for both parents born in Sweden vs. other countries, 1.21; 95% CI, 1.09-1.35, P < 0.001), and high maternal education level (Ptrend = 0.01). These risk factors did not vary by age at diagnosis. The association with high fetal growth appeared to involve pilocytic astrocytomas, but not other astrocytomas, medulloblastomas, or ependymomas. Gestational age at birth, birth order, multiple birth, and parental age were not associated with brain tumors. In this large cohort study, high fetal growth was associated with an increased risk of brain tumors (particularly pilocytic astrocytomas) independently of gestational age, not only in childhood but also into young adulthood, suggesting that growth factor pathways may play an important long-term role in the etiology of certain brain tumor subtypes.

Occupational exposure to extremely low-frequency magnetic fields and brain tumor risks in the INTEROCC study.

Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36-2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97-1.57; PLinear trend = 0.02). Results showed positive associations between ELF in the recent past and glioma. Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis.

Current State of Our Knowledge on Brain Tumor Epidemiology

The overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 person-years; 11.52 per 100,000 person-years for benign tumors and 7.19 per 100,000 person-years for malignant tumors. Incidence, response to treatment, and survival after diagnosis vary greatly by age at diagnosis, histologic type of tumor, and degree of neurologic compromise. The only established environmental risk factor for brain tumors is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor for brain tumor development. However, studies have been inconsistent and inconclusive due to systematic differences in study designs and difficulty of accurately measuring cell phone use. Recently studies of genetic risk factors for brain tumors have expanded to genome-wide association studies. In addition, genome-wide studies of somatic genetic changes in tumors show correlation with clinical outcomes.

Impact of random and systematic recall errors and selection bias in case-control studies on mobile phone use and brain tumors in adolescents (CEFALO study)

Whether the use of mobile phones is a risk factor for brain tumors in adolescents is currently being studied. Case--control studies investigating this possible relationship are prone to recall error and selection bias. We assessed the potential impact of random and systematic recall error and selection bias on odds ratios (ORs) by performing simulations based on real data from an ongoing case--control study of mobile phones and brain tumor risk in children and adolescents (CEFALO study). Simulations were conducted for two mobile phone exposure categories: regular and heavy use. Our choice of levels of recall error was guided by a validation study that compared objective network operator data with the self-reported amount of mobile phone use in CEFALO. In our validation study, cases overestimated their number of calls by 9% on average and controls by 34%. Cases also overestimated their duration of calls by 52% on average and controls by 163%. The participation rates in CEFALO were 83% for cases and 71% for controls. In a variety of scenarios, the combined impact of recall error and selection bias on the estimated ORs was complex. These simulations are useful for the interpretation of previous case-control studies on brain tumor and mobile phone use in adults as well as for the interpretation of future studies on adolescents.

CANCER: First Combined Analysis from INTERPHONE Inconclusive

CANCER: First Combined Analysis from INTERPHONE Inconclusive

Brain tumor susceptibility: the role of genetic factors and uses of mouse models to unravel risk.

Brain tumors are relatively rare but deadly cancers, and present challenges in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain, with surgery, radiation and chemotherapy options carrying potentially lasting morbidity for patients and incomplete cure of the tumor. The development of methods to prevent or detect brain tumors at an early stage is extremely important to reduce damage to the brain from the tumor and the therapy. Developing effective prevention or early detection methods requires a deep understanding of the risk factors for brain tumors. This review explores the difficulties in assessing risk factors in rare diseases such as brain tumors, and discusses how mouse models of cancer can aid in a better understanding of genetic risk factors for brain tumors.

Reproductive Factors and Risk of Meningioma and Glioma

Female sex hormones have previously been suggested as possible risk factors for brain tumors, but published studies have reported conflicting results. We conducted a population-based case-control study of glioma (n=626) and meningioma (n=906) cases and randomly selected controls stratified on age and geographic region (n=1,774) in Denmark, Finland, Norway, Sweden, and the United Kingdom. Unconditional logistic regression was used to estimate odds ratios (OR) for glioma and meningioma in relation to reproductive factors. A decreased glioma risk was associated with ever-pregnancy compared with never-pregnancy [OR, 0.8; 95% confidence interval (95% CI), 0.6-1.0]. Meningioma risk among women ages <50 years was increased in relation to number of pregnancies leading to a live birth (OR, 1.8; 95% CI: 1.1-2.8 for giving birth to 3 children compared with nulliparous women; P(trend) among parous women=0.01). This relation was not found for older women. Breast-feeding among parous women increased the glioma risk (OR, 2.2; 95% CI, 1.3-3.9 for breast-feeding 36 months or more compared with breast-feeding 3 months or less). Menopausal status and age at menopause were not associated with meningioma or glioma risk. Our findings imply that reproductive hormones may influence the occurrence of meningioma and glioma.

Environmental risk factors for brain tumors

Primary brain tumors, whether malignant or nonmalignant, have devastating consequences. Unfortunately, few known causes exist. Despite decades of epidemiologic research to identify environmental causes of brain tumors, very little progress has been made. The purpose of this paper is to review the most recent studies in the epidemiology of brain tumors. Popular topics of interest in adult brain tumor epidemiology include electromagnetic fields (particularly cellular phones), occupational exposures, nitroso-containing compounds (especially smoking), hair products, and allergic and immunologic factors. Some of these topics are also applicable to the etiology of childhood brain tumors, but additional areas of interest in the pediatric population focus on parental exposure prior to conception, maternal exposure during pregnancy, and childhood exposure to infectious agents. After an extensive review of the literature since 2001, we present the most relevant studies. Although there are many proposed associations with brain tumors, none possess the statistical significance to confidently ascribe causation. However, new findings and associations, particularly those in allergy and immunology, will present interesting opportunities for further development.

δ-Aminolevulinic Acid Dehydratase Polymorphism and Risk of Brain Tumors in Adults

The enzyme δ -aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case–control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls). Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6; 95% confidence interval (CI), 1.0–2.6], with the association appearing stronger in males (OR = 3.5; 95% CI, 1.3–9.2) than in females (OR = 1.2; 95% CI, 0.7–2.2). No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma.

Long-Term Follow-up for Brain Tumor Development after Childhood Exposure to Ionizing Radiation for Tinea Capitis

Ionizing radiation is an established risk factor for brain tumors, yet quantitative information on the long-term risk of different types of brain tumors is sparse. Our aims were to assess the risk of radiation-induced malignant brain tumors and benign meningiomas after childhood exposure and to investigate the role of potential modifiers of that risk. The study population included 10,834 individuals who were treated for tinea capitis with X rays in the 1950s and two matched nonirradiated groups, comprising population and sibling comparison groups. The mean estimated radiation dose to the brain was 1.5 Gy. Survival analysis using Poisson regression was performed to estimate the excess relative and absolute risks (ERR, EAR) for brain tumors. After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. The risk of both types of tumors was positively associated with dose. The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.

“Epidemiology of Health Effects of Radiofrequency Exposure”

In a recently published review (Kundi et al. 2004) on mobile phone use and cancer, we concluded that Epidemiological studies that approached reasonable latencies [time period between first exposure and diagnosis] consistently observed elevated risk for the development of neoplastic diseases. This assessment is distinctly different from the main message of the review from the International Commission for Non-Ionizing Radiation Protection (ICNIRP; Ahlbom et al. 2004). The authors stated that Results of these studies to date give no consistent or convincing evidence of a causal relation between RF [radiofrequency field] exposure and any adverse health effect. Although the use of subjective terms is sometimes unavoidable in the context of risk assessment (e.g., to evaluate sufficiency of evidence), the decision whether or not it evidence is “convincing” should be left to the reader. Furthermore, what constitutes consistent evidence or the lack of it is unclear when the scope is as broad as the authors implied in their reference to a “causal relation between RF exposure and any adverse health effect.” This review of epidemiologic evidence addressed the issue of causation without any consideration of the concept of causation in epidemiology, and it failed in its essential task to assess the possible association between exposure to RF and health. Concerning cancer, Moolgavkar and Luebeck (2003) have shown that agents that increase the growth rate of preneoplastic cells may have a distinctly greater impact on cancer incidence than agents that induce malignant transformation. However, this holds only for agents that act for prolonged periods of time. Regarding the natural history of cancer, a noticeable effect at the population level will only occur many years (and possibly decades) after first contact with the promoting agent. Although Ahlbom et al. (2004) pointed to the insufficient latencies in epidemiologic studies, they did not draw the straightforward conclusion—to assess the relationship between the latencies covered in the studies and their outcome. Although there is agreement between Ahlbom et al. (2004) and us (Kundi 2004; Kundi et al. 2004) that epidemiologic studies of RF/microwave exposure generally have deficiencies concerning exposure assessment, we must not ignore that the consequence of exposure misclassification is predominantly a bias of risk estimates towards the zero hypothesis. Another aspect that has contributed to, in our view, the inappropriate assessment of evidence is their view about the end points of the investigations. Among malignancies studied so far, the most heterogeneous group are brain tumors that comprise benign as well as malignant neoplasms with grossly different cellular origin, growth behavior, and fate. Until now no risk factor for brain tumors has firmly been established except ionizing radiation for meningeoma and menigeal sarcoma and less consistently for other brain tumors. Regarding brain tumors of high malignancy, little is known about induction periods and the steps necessary to reach the final invasive state; however, case reports of glioma after sellar irradiation (Simmons and Laws 1998) suggest an average induction period of about 10 years. Therefore, because exposure started too late for an effect during initiation and because proliferation is too fast for an effect on growth rate, brain tumors of highest malignancy must be studied very thoroughly in relation to latency, which was not the case for most of the studies published so far. Disregarding these conditions will strongly dilute any possible effect. Except for insufficient latency, other sources of possible bias were mentioned by Ahlbom et al. (2004), but again without consideration of the consequences on risk indicators. Ahlbom et al. (2004) stated that Several of these studies did not follow workers after they left the job of interest (Garland et al. 1990; Grayson 1996; Szmigielski 1996), with the potential for bias if individuals left employment because of health problems that subsequently turned out to be due to cancer.... The presence of this bias in these studies would have reduced the power in the case of no relation between exposure and the likelihood of leaving employment due to early signs of the target disease, or it would have led to a bias of risk estimates in the direction determined by the sign of the correlation between exposure and leaving service. It is quite likely that this correlation is positive because early signs of brain tumors will create problems in radio operators and also in personnel operating and maintaining radar equipment. Hence, the consequence of the bias is either reduction in the precision or inflation of risk estimates.

Reproductive and hormonal factors and risk of brain tumors in adult females

Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi-center case-control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency-matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09-3.32) for age at menarche > or =14 vs. <12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23-0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis.

Gliomas among men employed in the Swedish pulp and paper industry.

This study investigated whether previous findings of an increased risk of gliomas among workers in some pulp and paper mills could be confirmed for all Swedish pulp and paper mill workers and whether the increase could be attributed to certain occupational groups. The study was based on the Swedish Cancer Environment Register, which links the incidence of cancer from 1971 to 1990 and the 1960 and 1970 census data on codes of occupation and industry for the whole population. Standardized incidence ratios (SIR) were used to estimate the risks for men in different occupations in pulp (N = 28,142) and paper (N = 39,169) mills in 1960, 1970 or both years as compared with those of all gainfully employed men in Sweden. Maintenance workers employed in pulp or paper mills in 1960, 1970 or both years, as well aspulp workers, showed an increased incidence of gliomas in 1971-1990 [SIR 1.5, 95% confidence interval (95% CI) 1.1-2.1 and SIR 1.5,95% CI 1.0-2.2, respectively], whereas the incidence among process workers in paper mills was lower than expected (SIR 0.6, 95% CI 0.3-0.9). Taken together, all employed men in the pulp mill industry had an increased incidence of gliomas (SIR 1.3, 95% CI 1.0-1.7). Pulp mill workers, but not paper mill workers, were found to have more gliomas in 1971-1990 than expected. There was an increased risk of gliomas among maintenance workers in both pulp and paper mills. Few risk factors for brain tumors are recognized, and the causes of the increase are not obvious.

Contacts with animals and humans as risk factors for adult brain tumours. An international case–control study

While numerous studies have addressed the possible role of farming and related exposures as risk factors for brain tumours in adults, few of them have examined the potential effect of exposure to farm animals or pets. In an international multicentre case–control study, we investigated whether residence on a farm, contact with animals, or working in occupations with a high degree of potential contact with animals or humans were associated with brain tumours. Using a common questionnaire, 1177 cases of glioma, 330 with meningioma and 2478 controls from eight centres were interviewed about the exposures and, in particular, about their contacts with nine species of animals: dairy cattle, beef cattle, pigs, horses, sheep, goats, poultry, dogs and cats. Living or working on a farm was not a risk factor, for either glioma or meningioma. Except in some centres, there was no relationship between having contacts with farm animals or pets and the risk of brain tumour, for either type of tumour or either sex. In relation to seven industrial groups involving frequent human and/or animal contacts, no association was apparent for either glioma or meningioma. In relation to 25 occupational groups with potential frequent contact with humans and/or animals, for glioma there was a reduced risk for biological technicians (Odds Ratio (OR)/=0, P=0.01), and general farm workers (OR=0.66, 95% Confidence Interval (CI): 0.5–0.9). For meningioma, there was an increased risk for cooks (OR=2.0; CI: 1.2–3.4). With some exceptions, these results indicate no association between either the type of brain tumour and contacts with animals, or with occupations that include a high level of contact with animals or a high level of contact with humans.