Brain Cancer Cases Research Articles

Real-time Quantitative RT-PCR for CT9 Level in Human Cancer

CT9 is a recently cloned cancer-testis antigen, which is a member of the bromodomain and extraterminal family. Each member of this protein family contains two N-terminal bromodomain motifs. We investigated the distribution of CT9 in different tissues and the possibility for it to be used as a potential therapeutic target in cancer treament. By using the real-time RT-PCR method and 18SrRNA as an internal standard, we analyzed the CT9 expression in several normal human tissues and in the tissues of patients suffering from cancer. The result of this study shows that the highest level of mRNA is only present in testis tissue because the CT9 expression has not been detected in other normal tissues. In 6 of 10 cases of gastric adenocarcinoma, in 3 of 10 cases of esophageal squamous cell carcinoma, in 2 of 9 cases of endometrial carcinoma and only in 1 of 12 cases of brain cancer, the low level expression of CT9 was detected. In none of the 12 cases of cervical squamous cell carcinoma, the expression of CT9 was detected. Since the high level expression of CT9 is only found in the normal testis tissue, but the low expression in cancer tissues, for example tissues of cervical squamous cell carcinoma, brain cancer, endometrial adenocarcinoma, esophageal squamous cell carcinoma, we conclude that CT9 cannot be used as a cancer therapeutic target molecule for cervical squamous cell carcinoma, brain cancer, endometrial adenocarcinoma, esophageal squamous cell carcinoma.

Occupational Risk Factors for Brain Cancer in Canada

We sought to examine the impact of occupational exposure on brain cancer risk. Mailed questionnaires were used to collect information on lifetime employment history, occupational exposure to 18 chemicals, and other risk factors for 1009 incident cases of brain cancer and 5039 control subjects in Canada in 1994 to 1997. People exposed to asphalt and welding had respective odds ratio (and 95% confidence interval) of 1.29 (1.02-1.62) and 1.26 (0.98-1.45). An increased risk of brain cancer might be associated with exposure to asbestos, benzene, mineral or lubricating oil, isopropyl oil, and wood dust and with following occupations: teaching; protective service; metal processing and related jobs, and metal shaping and forming; knitting in textile processing; construction trades; and transport equipment operating. Our study suggests a possible role for occupational exposure in the etiology of brain cancer.

The familiality of primary brain tumors as studied in the Utah Population Database (UPDB)

1526 Background: The UPDB is a unique database linking 2.5 million Utah individuals with genealogical data to 80,000 Utah SEER cancer registry records since 1973. The familial nature of cancer has been well studied using this resource. Here we use similar techniques to investigate 1550 individuals diagnosed with brain tumors. Methods: We estimated the relative risk of brain cancer in relatives of brain cancer cases using internal age- and sex-specific rates of brain cancer estimated from UPDB. We estimated the average relatedness of brain cancer cases (compared to the average relatedness for 1000 matched control groups) using the Genealogical Index of Familiality measure, which extends beyond first degree relatives and looks at all pair wise relationships between cases. We considered all 1550 brain cancers as a group, the subgroup of 364 astrocytomas and the subgroup of 571 glioblastomas. Results: The relative risk for brain cancer in 1st degree relatives of all brain cancer cases is 2.78 (p=5.1xe-7). The...

The familiality of primary brain tumors as studied in the Utah Population Database (UPDB)

1526 Background: The UPDB is a unique database linking 2.5 million Utah individuals with genealogical data to 80,000 Utah SEER cancer registry records since 1973. The familial nature of cancer has been well studied using this resource. Here we use similar techniques to investigate 1550 individuals diagnosed with brain tumors. Methods: We estimated the relative risk of brain cancer in relatives of brain cancer cases using internal age- and sex-specific rates of brain cancer estimated from UPDB. We estimated the average relatedness of brain cancer cases (compared to the average relatedness for 1000 matched control groups) using the Genealogical Index of Familiality measure, which extends beyond first degree relatives and looks at all pair wise relationships between cases. We considered all 1550 brain cancers as a group, the subgroup of 364 astrocytomas and the subgroup of 571 glioblastomas. Results: The relative risk for brain cancer in 1st degree relatives of all brain cancer cases is 2.78 (p=5.1xe-7). The average relatedness of all brain cancers was significantly higher than expected in controls (p=0.03). The relative risk for brain cancer in 1st degree relatives of cases with astrocytoma was 3.03. The astrocytoma subgroup also showed significantly higher average relatedness than controls (p=0.002). The relative risk of all brain cancers in the first-degree relatives of glioblastoma cases was 2.60 (p=2.0xe-3). The glioblastoma subgroup of cases did not show significantly higher average relatedness than expected in controls (p=0.68). Conclusions: The UPDB resource provides strong evidence for a familial component in brain cancer that seems to extend beyond first-degree relatives. The subgroup of astrocytoma showed more evidence for underlying genetic component than the glioblastoma subgroup. Study of high-risk pedigrees could allow increased understanding of brain cancer predisposition genes. No significant financial relationships to disclose.

Brain cancer and cosmetic breast implants: a review of the epidemiologic evidence.

Recently, the findings of 1 mortality follow-up study have raised concern regarding the risk of brain cancer among women with cosmetic breast implants. In this review, the authors examine the results of 4 existing large-scale incidence follow-up studies comprising more than 10,000 women with cosmetic implants followed for as long as 29 years. Overall, there were 12 observed incident cases of brain cancer compared with 9.6 cases expected, yielding a nonstatistically significant summary standardized incidence ratio of 1.25 (95% confidence interval, 0.7-2.2). Based on the confidence interval alone, this result rules out the standardized mortality ratio of 2.45 reported in the 1 positive mortality study. Overall, the epidemiologic evidence does not support an association between breast implants and brain cancer incidence.

Brain Cancer in a Residential Area Bordering on an Oil Refinery

Both in response to community concerns about brain cancer related to an oil refinery and in order to more fully understand the etiology of primary site brain cancer (glioma), a highly focused cancer cluster investigation was conducted. The components included: (1) a literature review of occupational exposures in the petroleum refining and petrochemical industries, (2) comparisons between observed and expected cases, (3) comparisons between mean age at diagnosis and median survival time and (4) interviews concerning exposures of cases. Evidence from the literature review revealed little, if any, effect of petroleum refinery or petrochemical exposure on the risk for brain cancer. There was no statistically significant increase in the number of brain cancer cases in the community (observed = 12, expected = 9.46, standardized mortality ratio = 1.27). There was no statistically significant decrease in mean age at diagnosis or median survival time among those most exposed. Reports of exposure from the case interviews were highest for eating processed meats (98.5%), dental X-rays (96.6%), dog ownership (91.2%) and swimming (80.3%). There were no major occupational exposures identified. It seems unlikely that petrochemicals are involved in any significant way in the etiology of most brain cancers (gliomas). A follow-up case-control study should focus primarily on those risk factors mentioned frequently by the cases.

Cancer risks in populations living near landfill sites in Great Britain.

Previous studies have raised concerns about possible excess risks of bladder, brain and hepatobiliary cancers and leukaemias near landfill sites. Several cancers have been implicated, but no consistent pattern has emerged. We present a large nationwide analysis of selected cancers near landfill sites in Great Britain. The base population comprised people living within 2 km of 9565 (from a total of 19 196) landfill sites that were operational at some time from 1982 to 1997, with populations living more than 2 km from a landfill as reference. Risks of cancers at the above sites were computed with adjustment for age, sex, year of diagnosis, region and deprivation. National post-coded registers provided a total of 341 856 640 person–years for the adult cancer analyses and 113 631 443 person–years for childhood leukaemia. There were 89 786 cases of bladder cancer, 36 802 cases of brain cancer, 21 773 cases of hepatobiliary cancer, 37 812 cases of adult leukaemia and 3973 cases of childhood leukaemia. In spite of the very large scale of this national study, we found no excess risks of cancers of the bladder and brain, hepatobiliary cancer or leukaemia, in populations living within 2 km of landfill sites. The results were similar if the analysis were restricted to landfill sites licensed to carry special (hazardous) waste. Our results do not support suggestions of excess risks of cancer associated with landfill sites reported in other studies.British Journal of Cancer (2002) 86, 1732–1736. doi:10.1038/sj.bjc.6600311 www.bjcancer.com© 2002 Cancer Research UK

Brain cancer risk and electromagnetic fields (EMFs): assessing the geomagnetic component.

Cancer cluster studies in North Carolina identified several communities in which there existed an elevated risk of brain cancer. These findings prompted a series of case-control studies. The current article, which originated from the results of the 3rd of such studies, is focused on inclusion of the earth's own geomagnetic fields that interact with electromagnetic fields generated from distribution power lines. This article also contains an assessment of the contribution of confounding by residential (e.g., urban, rural) and case characteristics (e.g., age, race, gender). Newly diagnosed brain cancer cases were identified for a 4-county region of central North Carolina, which the authors chose on the basis of the results of earlier observations. A 3:1 matched series of cancer cases from the same hospitals in which the cases were diagnosed served as the comparison group. Extensive geographic information was collected and was based on an exact place of residence at the time of cancer diagnosis, thus providing several strategic geophysical elements for assessment. The model for this assessment was based on the effects of these two sources of electromagnetic fields for an ion cyclotron resonance mechanism of disease risk. The authors used logistic regression models that contained the predicted value for the parallel component of the earth's magnetic field; these models were somewhat erratic, and the elements were not merged productively into a single statistical model. Interpretation of these values was difficult; therefore, the modeled values for the model elements, at progressive distances from the nearest power-line segments, are provided. The results of this study demonstrate the merits of using large, population-based databases, as well as using rigorous Geographic Information System techniques, for the assessment of ecologic environmental risks. The results also suggest promise for exposure classification that is compatible with the theoretical biological mechanisms posited for electromagnetic fields.

Refinements in magnetic field exposure assignment for a case-cohort study of electrical utility workers.

This study examined the effect of refinements in exposure assignment on annual and career exposure to 60 Hz magnetic fields, using all deaths from brain cancer (145) and leukemia (164) and a random sample of 800 workers from a cohort of 138,905 men. Reassessment of 1060 job titles in the measurement database generated 20 subcategories in addition to 28 occupational categories used in the original cohort mortality study. Furthermore, previously misclassified jobs were corrected. The complete work history of each sub-cohort member was re-examined. Original and refined average annual exposures were 0.086 and 0.088 microT, respectively. The average career cumulative exposures were 1.40 and 1.44 microT-years, respectively. Spearman correlation coefficients between the original and refined methods across the companies were 0.81 for annual exposure and 0.93 for career cumulative exposure. 23% of the workers were assigned to another exposure ranking after refinement, but 85% of these moved to an adjacent group, suggesting that the differences in exposure ranking are small. The results of this study indicate that refinements have modest influence on the average annual and career exposures. However, the refinements may only change a very rough exposure assessment into one that is slightly less crude. The proportion of workers assigned to another exposure ranking indicated that nondifferential exposure misclassification in the original cohort mortality study may have occurred. Implications of these changes for the risk estimates of brain cancer and leukemia cases will to be examined.

Refinements in magnetic field exposure assignment for a case-cohort study of electrical utility workers

This study examined the effect of refinements in exposure assignment on annual and career exposure to 60 Hz magnetic fields, using all deaths from brain cancer (145) and leukemia (164) and a random sample of 800 workers from a cohort of 138 905 men. Reassessment of 1060 job titles in the measurement database generated 20 subcategories in addition to 28 occupational categories used in the original cohort mortality study. Furthermore, previously misclassified jobs were corrected. The complete work history of each sub-cohort member was re-examined. Original and refined average annual exposures were 0.086 and 0.088 μT, respectively. The average career cumulative exposures were 1.40 and 1.44 μT-years, respectively. Spearman correlation coefficients between the original and refined methods across the companies were 0.81 for annual exposure and 0.93 for career cumulative exposure. 23% of the workers were assigned to another exposure ranking after refinement, but 85% of these moved to an adjacent group, suggesting that the differences in exposure ranking are small. The results of this study indicate that refinements have modest influence on the average annual and career exposures. However, the refinements may only change a very rough exposure assessment into one that is slightly less crude. The proportion of workers assigned to another exposure ranking indicated that nondifferential exposure misclassification in the original cohort mortality study may have occurred. Implications of these changes for the risk estimates of brain cancer and leukemia cases will to be examined.

Diet and brain cancer in adults: a case-control study in northeast China.

A hospital-based case-control study was conducted in the Heilongjiang Province of northeast China between May 1993 and May 1995. A total of 129 histologically confirmed brain cancer cases (73 gliomas and 56 meningiomas) and 258 matched controls were interviewed in 6 major hospitals to examine the influence of dietary factors in developing brain cancer. Information was obtained about frequency of consumption of 57 food items. Odds ratios (ORs) were obtained from conditional logistic regression, including allowance for socio-demographic factors, alcohol, tobacco and total energy intake. Consumption of fresh vegetables (OR = 0.29 for the highest quartile compared with the lowest one), and specifically of Chinese cabbage and onion, fruit (OR = 0.15), fresh fish (OR = 0.38) and poultry (OR = 0.16) was inversely related to the risk of developing brain cancer. A protective effect was also seen for vitamin E intake, calcium and, although non-significantly, beta-carotene and vitamin C. Risk of brain cancer increased with consumption of salted vegetables (OR = 2.54) and salted fish.

Evidence for a Rare Prostate Cancer–Susceptibility Locus at Chromosome 1p36

Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.

Brain cancer and occupational exposure to lead.

A recent report in the literature suggested a link between occupational exposure to lead and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992. Brain cancer risk increased by probability of exposure to lead among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lead (odds ratio = 2.1; 95% confidence interval, 1.1-4.0). Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined). Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis.

Pesticide Prioritization for a Brain Cancer Case-Control Study

The incidence of brain cancer is rising in the United States while the causes remain largely unknown. Epidemiologic studies indicate that individuals working in agriculture have an increased risk of brain cancer. The National Institute for Occupational Safety and Health is conducting a case-control study of incident brain cancer cases in Iowa, Michigan, Minnesota, and Wisconsin to evaluate the risk associated with several environmental exposures, in particular agricultural pesticides. Hundreds of different pesticides are used in agriculture and it is not feasible to evaluate the association between brain cancer and exposure to each of these chemicals; therefore, a strategy was developed to identify which pesticides would be targeted in the study. First, lists of pesticides were created, documenting usage in each of the four states and the United States as a whole, by using data from reports prepared by the U.S. Department of Agriculture and Departments of Agriculture and land grant colleges within the four states. Then the following factors were considered in prioritizing pesticides for evaluation in the study: total volume of use prior to 1985, ranking of use in the four states and the United States as a whole by pesticide category, and toxicological evidence of carcinogenic, teratogenic, or mutagenic effects. Pesticide usage prior to 1985 was determined to allow for a minimum 10-year latency for the incident brain cancer cases diagnosed in 1995 or later. The selected pesticides include 56 herbicides, 49 insecticides, 12 fungicides, and 17 fumigants, accounting for over 99% of the total pounds of herbicides and insecticides and over 98% of the total pounds of fungicides and fumigants applied pre-1985. Prompt lists of the pesticides are sent to study participants a few days before the study questionnaire is administered to allow them time to recall past use of pesticides; the lists include the common chemical names, trade names, the crops that the pesticides are most commonly used on, and the years that the pesticides have been marketed. The methods used to select this subset of 134 pesticides document historical pesticide usage and may be useful in prioritizing pesticides for other research studies.

Occupational exposure to magnetic fields in relation to mortality from brain cancer among electricity generation and transmission workers.

OBJECTIVE: To investigate whether the risks of mortality from brain cancer are related to occupational exposure to magnetic fields. METHODS: A total of 112 cases of primary brain cancer (1972-91)...

Interpretation of secular increases in incidence rates for primary brain cancer in Connecticut adults, 1965-1988.

Available summaries of radiology reports were examined among 899 primary brain cancer cases (age 40 years and older) diagnosed in Connecticut residents in selected years from 1965 to 1988 and reported to the population-based Connecticut Tumor Registry. Adjustment for the lower sensitivities of radiologic tests used before the advent of computerized tomography (CT) suggested that the introduction of CT (by itself) could account for little of the secular increase in brain cancer rates. Examination of trends in age-standardized rates for histologically confirmed brain cancers in the elderly, after excluding those diagnosed only by radiologic tests, did not support the idea that the secular trend in the elderly was largely artifactual.

Mortality study among workers producing chromate pigments in France.

In a follow-up study of 294 men who had worked for at least 6 months in a chromate-producing factory in France between 1958 and 1987, only 16 were lost to follow-up and the number of person-years in the study was 5207. Occupational data were provided by the administration of the plant. The causes of deaths were ascertained from hospital and general practitioners' records. The observed numbers of deaths were compared with the expected numbers based on local rates with adjustment for age, sex and calendar time (standardized mortality ratio, SMR). The overall mortality did not differ significantly from that expected (SMR = 1.20, 95% CI = 0.98-1.47), whereas mortality due to lung cancer was in significant excess (SMR = 3.60, 95% CI = 2.13-5.68). Significantly higher lung cancer SMRs were found for workers whose duration of employment was more than 10 years. A non-significant excess was observed for all forms of digestive tract cancer (SMR = 1.30, 95% CI = 0.60-2.47). There were two cases of brain cancer when 0.24 was expected (SMR = 8.44, 95% CI = 1.02-30.49). No previous report has mentioned an association of brain cancer with chromate pigments; however, because of the small numbers involved, a chance excess should be considered.

Hydrogen magnetic resonance spectroscopy follow-up after radiation therapy of human brain cancer. Unexpected inverse correlation between the changes in tumor choline level and post-gadolinium magnetic resonance imaging contrast.

The anatomic and metabolic changes in human brain tumors treated by radiation therapy were compared using gadolinium-enhanced magnetic resonance imaging and hydrogen (1H) magnetic resonance spectroscopy. The study was intended to assess the potential of 1H magnetic resonance spectroscopy in monitoring response to therapy. Thirteen cases of brain cancer treated by radiation therapy were examined by 1H magnetic resonance spectroscopy and gadolinium-enhanced T1-weighted magnetic resonance imaging and reexamined at 2-month intervals. Follow-up after radiation therapy showed changes in post-gadolinium magnetic resonance imaging contrast that are inversely correlated with the changes in choline level (r = -0.69, P < 0.00001) and in tumor volume (r = -0.35, P < 0.05). The choline loss in tumors gaining post-gadolinium magnetic resonance imaging contrast after therapy is unexpected in view of previously reported correlation between the two in untreated metastatic brain tumors. Indicated is the use of 1H magnetic resonance spectroscopy to discriminate enhancing brain tumors with a high content of vital tumor cells (high choline) from tumors, combining decreased cell density with increased interstitial space (low choline).

Brain cancer incidence, mortality and case survival: observations from two Australian cancer registries.

Data from 2 Australian cancer registries covering a population of 1.7 million people were combined for the purposes of analysing brain cancer incidence, mortality and survival patterns for the time period 1978 through 1992. A total of 1,752 cases of primary brain cancer were registered, representing age-standardised incidence rates of 6.7 per 100,000 in men and 4.6 in women. Histological confirmation was available for 94% of cases. The incidence rate among persons aged 75 or over was higher during 1986-1992 than during 1978-1985, the rate for men increasing from 16.3 to 26.2 and that for women increasing from 9.7 to 18.0. The largest increases in this age group occurred for cases of glioblastoma multiforme. During the study period, 1,411 brain cancer deaths were notified to the 2 registries at age-standardised rates of 5.3 in men and 3.4 in women. Mortality rates among persons aged 75 years or older were higher during 1986-1992 than 1978-1985, increasing from 15.7 to 28.4 in men and from 10.1 to 15.3 in women. Only among men aged 15-49 years was a decline in mortality rates observed, from 3.3 to 2.4. Survival analyses indicated that age and histological type were the most powerful prognostic indicators. There was no improvement in 5-year survival for any of the age groups or histological types. An improvement in 36-month survival was noted for the 15-49 year age group diagnosed with gliomas other than glioblastoma multiforme.

Birth characteristics of childhood cancer cases, controls, and their siblings.

Reproductive characteristics of childhood cancer cases, controls, and their siblings were examined using data from a case-control study in the Denver, Colorado metropolitan area. Childhood cancer patients (n = 356) diagnosed from 1976 to 1983 were identified, and 242 were interviewed. Controls were selected by random digit dialing, with 212 interviews being completed (60% of eligibles). Extremes of birth weight were more common only among brain cancer cases. Patients were more often born preterm, particularly those with brain tumors [odds ratio (OR) = 6.1; 95% confidence interval (CI), 1.6-23.4] and were more likely to have birth defects (OR = 2.1; 95% CI, 0.9-5.0). Twins were more common among case siblings (OR = 2.6; 95% CI, 0.8-8.2). Low birth weight and preterm delivery among siblings were related only to soft tissue sarcoma. Birth defects were more common among case siblings, particularly leukemia cases (OR = 3.2; 95% CI, 1.3-7.7). Previous reports of elevated birth weight among cases and increased risk of miscarriage in case mothers were not corroborated, but associations with preterm delivery, high birth order, and birth defects among cases and birth defects and twinning among cases siblings encourage additional evaluation.