Risk Factors For Brain Tumors Research Articles

Gamma-radiation sensitivity and risk of glioma.

About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001). gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.

High frequency of the H63D mutation of the hemochromatosis gene (HFE) in malignant gliomas

Risk factors for brain tumors, except for ionizing radiations, remain substantially unknown.1 Iron exposure could be among these factors, as in vitro iron may promote the growth of malignant gliomas2 and iron chelators can inhibit this growth.3 Excess iron can favor the generation of highly reactive hydroxyl radicals, which, in turn, may cause point mutations in genomic DNA. Furthermore, increased levels of non-heme iron can convert nitric oxide from a proapoptotic to an antiapoptotic molecule. Notably, the c-myc oncogene, which is also expressed in high-grade gliomas, modulates the expression of genes controlling iron homeostasis, increasing the availability of intracellular iron.4 The hereditary hemochromatosis gene ( HFE ) has a critical role in iron homeostasis and two mutations of this gene, C282Y and H63D, are …

Occupational risk factors for brain tumours in adults. Results from the international brain tumour case- control study

Occupational risk factors for brain tumours in adults. Results from the international brain tumour case- control study

Parental cancer as a risk factor for brain tumors (Sweden).

We used the nationwide Swedish Family-Cancer Database to analyze the risk for adult (15-61 years) brain tumors in offspring through parental cancer probands. Additionally, cancer risks were assessed among siblings of brain tumor probands. In offspring and parents, respectively, 5,425 and 20,938 cases of brain tumors were diagnosed between the years 1958 and 1996. Groups of offspring were compared by calculating standardized incidence ratios (SIRs) for brain tumors. Of brain tumor patients, 2.1% had a parent with nervous system cancer; SIRs were 1.7, 2.4, and 2.5 for all brain tumors, astrocytomas, and meningiomas, respectively. Parental endometrial cancer and melanoma were associated with offspring astrocytoma, and parental breast and thyroid cancers with offspring ependymoma and neurinoma, respectively. SIR for sibling nervous system tumors from brain tumor probands was not increased overall but was 2.5 in those diagnosed at ages 15-34 years. These data show a familial risk for brain tumors among adults.

Are Prior Head Injuries or Diagnostic X-Rays Associated with Glioma in Adults? The Effects of Control Selection Bias

The causes of glioma, the most common type of primary malignant brain tumors, are poorly understood. This study compares personal histories of head injury and diagnostic radiation procedures of the head and neck among 476 adults newly diagnosed with glioma in the San Francisco Bay Area between August of 1991 and April of 1994 (82% of all those diagnosed during that time period) with 462 age-, gender-, and ethnicity-frequency-matched controls (63% of those eligible from random digit dialing). In addition, limited information was obtained from 101 controls during a brief telephone interview conducted with controls who declined participation in the lengthy in-person interview. Controls who participated in the full interview were much more likely than controls who only completed the telephone interview to report head injury [odds ratios (OR) and 95% confidence intervals (CI) were 2.3 (1.0–4.9) and 3.0 (1.6–5.8) for women and men, respectively]. The OR for any head injury in cases versus controls who completed the full interview was 0.9. However, OR for any head injury in cases versus both control groups was 1.3, 95% CI (1.0–1.7), and the OR for head injury for which the subject sought medical attention was 1.1, 95% CI (0.8–1.4). Among subjects completing the full interview, cases who responded by self-report were less likely than controls to report prior non-dental head and neck X-rays (OR = 0.7; 95% CI: 0.5–1.0). However, stratification by respondents’ history of head injury indicated no difference in history of head and neck X-ray among those without prior head injury; OR 0.9; 95% CI (0.6–1.2). Cases and controls shared a very similar history of dental procedures and frequency of dental visits. These results suggest that head injury requiring medical attention, dental visits, or non-dental diagnostic X-rays to the head and neck are not important contributors to the risk of adult glioma and reveal some of the methodological obstacles encountered in forming convincing conclusions about these risk factors for brain tumors.

Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case-control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age ≥ 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the eases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene-environment interactions.

Nutritional Factors in the Etiology of Brain Tumors Potential Role of Nitrosamines, Fat, and Cholesterol

Several possible risk factors for brain tumors have been suggested in the past, including N-nitroso compounds, but with the exception of ionizing radiation, none has been consistently confirmed. The present study was aimed at assessing the influence of nutritional factors, including N-nitroso compounds, in the etiology of brain tumors, specifically gliomas and meningiomas. One hundred and thirty-nine cases with confirmed brain tumors diagnosed between 1987 and 1991 in central Israel and 278 controls matched according to age, sex, and ethnic origin were interviewed. Nutritional data were obtained using a semiquantitative food frequency approach. A significant positive association for both types of brain tumors was found with high protein intake (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.03-3.63), while intake of sodium was inversely related to both types of brain tumors (OR = 0.52, 95% CI 0.31-0.87). Increased consumption of total fat and cholesterol was inversely related to gliomas (high intake of fat: OR = 0.45, 95% CI 0.20-1.07; high intake of cholesterol: OR = 0.38, 95% CI 0.14-1.01). However, neither fat intake nor cholesterol intake was significantly related to the risk of meningiomas. Although N-nitroso compounds were not found to be directly associated with brain tumors, the data suggested the presence of an interaction between the effects of N-nitroso compounds and protein intake and between N-nitroso compounds and cholesterol intake. The data suggest that dietary factors may play an important, though yet undefined, role in the development of brain tumors.

Head Injury as a Risk Factor for Brain Tumors in Children: Results from a Multicenter Case-Control Study

We evaluated the risk of brain tumor occurrence in relation to previous head injury in a population-based case-control study of 540 children with a primary brain tumor and 801 control children. The risk of a brain tumor among children with a previous head injury that resulted in medical attention was slightly elevated when compared with children with no reported head injury [odds ratio (OR) = 1.4; 95% confidence limits (CL) = 1.0, 1.9]. This effect was stronger when we restricted the head-injured group to the few children with loss of consciousness (OR = 1.6; 95% CL = 0.6, 3.9) or an overnight admission to a hospital (OR = 1.7; 95% CL 0.7, 4.6), relative to those with no head injury. We observed no appreciable association between brain tumor occurrence and birth injury involving the head or a forceps delivery. Among the few children with either a birth injury or forceps delivery and a subsequent head injury, we observed approximately twofold elevations in risk. The OR was 2.6 (95% CL = 1.1, 6.9) for those with a birth injury and subsequent head injury, relative to those with neither a birth injury nor head injury. Our results provide only weak evidence in support of head injury as an etiologic agent for brain tumor occurrence in children, although most of our exposed group had only mild head injury.

Development of intracranial tumors in patients with long-standing preexisting epilepsy

We report 8 patients who had an intracranial tumor intercurrently with long-standing preexisting epilepsy. In 4 [3 idiopathic generalized epilepsies (IGE), 1 frontal lobe epilepsy (FLE)], the tumor was extracerebral or subcortical (2 craniopharyngiomas, 1 germinoma, 1 meningioma) and did not affect the course of epilepsy. In 4 [1 IGE, 2 FLE, 1 temporal lobe epilepsy (TLE)], the tumor was superficial and intracerebral (3 astrocytomas, 1 oligodendroglioma) and the first sign of tumor was a change in the intensity or symptoms of epilepsy. Diagnosis of the tumor was delayed in the second group. Clinical and biologic evidence suggest that epilepsy and antiepileptic drugs are not risk factors for brain tumors. However, clinicians should bear in mind that not all brain tumors cause epileptic seizures and that patients with various types of epilepsy can develop brain tumors. Aggravation or change in the symptomatology of epilepsy warrants thorough investigation to rule out the possibility of development of an intercurrent brain tumor.

Association of malignant brain tumors and cancers of other sites.

We conducted an exploratory study of brain tumors that occurred as a second primary malignancy to identify potential risk factors for brain tumors. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated the sex-specific standardized incidence ratio (SIR), adjusted to age and time period, as an estimate of the relative risk (RR) of developing a second primary brain tumor following other cancers. We found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7; 95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to 3.2); this effect was present for both astrocytoma and glioblastoma multiforme. Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8 to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0 to 1.9) in women. The highest RR observed in this study was for CNS lymphoma following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0). The associations of brain tumors with bladder, colorectal, and endometrial cancers in women, and an increased occurrence of CNS lymphoma as a second malignancy in men, are new findings that have not been described previously.

Occupational risk factors for brain tumors among women in Shanghai, China.

The etiology of brain cancer is not well understood and few studies have evaluated occupational risk factors among women. We evaluated occupation and industry at time of diagnosis for 276 incident primary brain tumor cases among women in Shanghai, China, for the period 1980-1984, identified through the Shanghai Cancer Registry. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were calculated for all occupations and industries with at least three female cases. SIRs compared observed to expected numbers of cases, based on incidence rates for Shanghai and the number of women in each occupation and industry according to the 1982 census. Statistically significant excesses of brain tumors were seen among grain farmers (SIR = 6.5, 95% CI = 1.3-19.1), rubber workers (SIR = 5.0, 95% CI = 1.6-11.6), and workers in transportation equipment manufacture and repair (SIR = 2.3, 95% CI = 1.1-4.3). Risks among textile spinners and winders were of borderline significance (SIR = 1.7, 95% CI = 1.0-2.8). Elevated but nonsignificant risks of 2.0 or greater were seen among nurses, plastic products workers, sanitation workers, painters, and workers in manufacture of equipment for electrical generation, transmission, and distribution. Results for farmers, rubber workers, and painters are consistent with previously reported excesses among these occupations in men. The increase among nurses is a new finding, although elevated risks have been observed among male medical professionals. Risks were elevated with likely exposure to pesticides, particularly among those thought to have a high probability and a high level of exposure (SIR = 3.6, 95% CI = 1.2-8.5).

Relation between maternal diet and subsequent primitive neuroectodermal brain tumors in young children.

It has been hypothesized that a high dietary intake of nitrosamines and their precursors, nitrites and nitrates, is a risk factor for brain tumors. Vitamins C and E inhibit the formation of nitrosamines and thus may be protective. We conducted a case-control study of maternal diet and the risk of primitive neuroectodermal tumors of the brain in children. The case patients were under the age of six years at diagnosis in 1986 to 1989. The controls were selected by random-digit telephone dialing and were matched for age and race to 166 case patients. Telephone interviews with the mothers included questions on the frequency of consumption of alcohol, vitamin and mineral supplements, and 53 foods during pregnancy. Significant protective trends were observed for vegetables (odds ratio for the highest quartile group for intake relative to the lowest, 0.37; P for trend = 0.005), fruits and fruit juices (odds ratio, 0.28; P = 0.003), vitamin A (odds ratio, 0.59; P = 0.03), vitamin C (odds ratio, 0.42; P = 0.009), nitrate (odds ratio, 0.44; P = 0.002), and folate (odds ratio, 0.38; P = 0.005). A nonsignificant trend of increasing risk was observed for nitrosamine (odds ratio, 1.65; P = 0.15). The use of iron (odds ratio, 0.43; P = 0.004), calcium (odds ratio, 0.42; P = 0.05), and vitamin C (odds ratio, 0.35; P = 0.04) supplements at any time during the pregnancy and the use of multivitamins during the first six weeks (odds ratio, 0.56; P = 0.02) were associated with decreased risk. In multivariate analyses, folate, early multivitamin use, and iron supplements generally remained protective. These results do not support the hypothesis that nitrosamines have a role in the development of primitive neuroectodermal tumors in young children, but they do suggest that certain other aspects of maternal diet can influence the risk.

Environmental risk factors for primary malignant brain tumors: a review.

This review suggests that existing theories of carcinogenesis provide much of the necessary framework for understanding the etiologies of malignant gliomas. Most of the environmental risk factors associated with brain tumors involve exposures to infectious, chemical, or physical agents capable of inflicting genetic damage. It is equally important to recognize that some potential risk factors for brain tumors, if their association proves causal, suggest as yet unknown or undefined mechanisms of carcinogenesis. For example, the mechanisms through which extremely-low-frequency electromagnetic fields might induce cancer are unknown, but interest in this area is intensifying [165]. Large population based studies currently being conducted throughout the world will help to estimate the relative importance of some suspected factors. Several of the most serious limitations of previous studies can be overcome by careful study design including sample size planning to ensure adequate power for important hypotheses and subgroup analyses, systematic pathology review to enable analyses by histologie type, collecting sufficiently detailed exposure data to minimize recall problems and permit flexibility in classifications, and using rapid case ascertainment systems to minimize the need for interviews with proxies and concomitant reporting bias. Furthermore, as important genes for brain tumors are identified, they can be used to further refine subtype classifications and to improve sensitivity in the search for environmental culprits.

Risk factors for tumors of the brain and meninges: Results from the Adelaide adult brain tumor study

A population-based case-control study of incident primary brain tumors in adults was carried out in Adelaide, Australia in the period 1987 through 1990. It included 110 subjects with newly diagnosed primary glioma, 60 subjects with meningioma and 417 controls selected from the Australian Electoral Roll and frequency-matched to cases for age (within 2 years), sex and postal code. Some interesting new associations were found: (1) an increased risk of glioma in women who reported working with cathode-ray tubes (relative risk = 4.1, 95% confidence interval: 1.3-13.2); (2) a decreased risk of glioma in those with a history of allergic diseases (relative risk = 0.5, 95% confidence interval: 0.3-0.9); and (3) an increased risk of meningioma in those exposed to passive smoking from a spouse, especially amongst females (relative risk = 2.7, 95% confidence interval: 1.2-6.1). A pooled analysis of the multi-center group of studies to which the present study belongs should allow more confident claims concerning risk factors for brain tumors.

Occupational risk factors for brain tumors: results from a population-based case-control study in Germany

In a population-based case-control study in the Rhein-Neckar-Odenwald area (containing 1.3 million inhabitants) of the Federal Republic of Germany (FRG), risk factors were assessed for brain tumor development in 226 cases with primary brain tumors (ICD-9 191, 192.1, 192.0) and 418 population controls, interviewed by a standardized questionnaire. The analysis of occupational risk factors and smoking is presented. No elevated risk was found for smoking. Similarly, no significant effects were found for most occupations. Five specific occupational groups were examined because of a priori determination that they were of interest. Some categories showed slightly elevated risks but in none was the elevation statistically significant. A significant increase in risk for brain tumor development was found associated with working in electrical occupations for women (relative risk [RR] = 5.2; 95 percent confidence interval [CI] 1.4-20.1) but not for men (RR = 0.9, 95 percent CI 0.3-2.3).

Potential risk factors for brain tumors in children

Two hundred cases of verified brain tumors occurring in patients under 15 years of age were studied in relation to possible etiologic, genetic, and environmental risk factors. They were compared with 100 age-matched patients harboring solid neoplasms outside the nervous system, as well as with 100 normal children. In our study, first-degree relatives of a brain tumor child did not show a higher incidence of either tumors or of epilepsy and strokes as compared with controls. First-born children (46%) with higher birth weights showed a greater tendency to present brain tumors. Dystocia (18.5%), previous miscarriages (18%), and dietary restrictions during pregnancy (3%) were also noted in this study and compared with data in the literature. No evidence of a role of maternal chickenpox and toxoplasmosis could be found. The pharmacological risk also seemed to be minimal. The mother's hormonal profile is deduced from the age at menarche and delivery, as well as from a tendency to miscarriages and complicated pregnancies. With regard to the immunologic aspect, it is worth noting that 15% of the mothers complained of allergies. Live polio vaccine and zoonosis might suggest a possible role of virus-related factors in the oncogenesis of brain tumors in children. Radiation-related risk is possibly present in less than 5% of cases. Parental occupation is not relevant in this series.

Occupational risk factors for brain tumors. A case-referent death-certificate analysis.

Numerous studies have suggested that employment in the oil refining and chemical manufacturing industries may be associated with excess brain tumor risk. A case-referent study was undertaken to evaluate brain tumor risk by occupation and industry in three geographic areas (northern New Jersey, Philadelphia, and the Gulf Coast of Louisiana) with a heavy concentration of these industries. Seven hundred and eighteen white men dying from brain tumor at age 30 years or older were ascertained from death certificates for 1978-1981. The referents were men who died of other causes, excluding epilepsy and stroke. Usual occupation and industry were obtained from the death certificates, and the maximum likelihood estimates of the relative risk were calculated for specific industries and occupations. Small nonsignificant excess risks of brain tumors were seen among persons whose usual employment was in the petroleum refining, electrical equipment manufacturing, health services, and educational services industries. Compared with other white-collar professionals, health diagnosticians, teachers, and artists/designers had a significantly elevated brain tumor risk. Among blue-collar workers, the only group with a significantly elevated brain tumor risk was precision metal workers, who are exposed to metal dusts and fumes and substances used as coolants, lubricants, and degreasers.