Brain Cancer Deaths Research Articles

Abstract 3173: Impact of hypoxia on the integrated stress response activated by imipridones ONC201 and ONC206 in pediatric diffuse midline glioma cells

Abstract Diffuse midline gliomas (DMGs) are highly aggressive, high-grade gliomas which typically arise in children and young adults. With currently approved treatments the median survival from time of diagnosis for pediatric DMG is 8-10 months with only 10% of children living to 2 years post diagnosis. Despite being only 15% of the cases it makes up 40% of the pediatric brain cancer deaths making it the leading cause of death for all pediatric glioma cases. Two recent clinical studies, NCT03416530 and NCT03134131, have shown the clinical efficacy of Dordaviprone (ONC201/TIC10) for the treatment of DMG; increasing median survival to 22 months in patients following radiation treatment prior to recurrence. Imipridone ONC206, a chemical derivative of ONC201, is under clinical development for treatment of pediatric and adult patients with primary brain tumors (NCT04732065 and NCT04541082). To further improve treatment, we must continue to study how the tumor microenvironment impacts the efficacy of imipridones. One crucial aspect of all brain cancers is hypoxia, so the IC50s of the SU-DIGP-25, SU-DIPG-XIII and SU-DIPGIV pediatric DMG cell lines treated with ONC201 or ONC206 were measured using the CellTiter-Glo assay under conditions of hypoxia and normoxia. Imipridones mediate apoptosis through the upregulation of the TRAIL death receptor DR5 and the activation of the integrated stress response (ISR), so western blots were used to show changes in the ISR protein expression in ONC201 treated DMG cells at multiple different degrees of hypoxia. To understand how hypoxia inducible factors (HIFs) play a role in resistance and susceptibility to ONC201 or ONC206, HIF-1a, HIF-2a, and HIF-3a were knocked down showing altered ISR protein expression after treating with the imipridones under hypoxic and normoxic conditions. Citation Format: Tyler J. Roady, Nolan Stubbs, Josephine Chen, Yutong Xia, Ashley Sanchez Sevilla Uruchurtu, Xiaobing Tian, Lanlan Zhou, Wafik S. El-Deiry. Impact of hypoxia on the integrated stress response activated by imipridones ONC201 and ONC206 in pediatric diffuse midline glioma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3173.

Brain Tumor Detection and Classification Using IFF-FLICM Segmentation and Optimized ELM Model

Brain cancer deaths are significantly increased in all categories of aged persons due to the abnormal growth of brain tumor tissues in the brain. The death rate can be controlled by accurate early stage brain tumor diagnosis. The detection and classification of brain tumors play a crucial role in early diagnosis and treatment planning. Brain tumor detection and classification have become challenging and time-consuming for domain-specific radiologists and pathologists in medical image analysis. So, automatic detection and classification are essential to reduce the time of diagnosis. In recent years, machine learning classifiers have played an essential role in automatically classifying brain tumors. In this research, an approach based on an improved fuzzy factor fuzzy local information C means (IFF-FLICM) segmentation and hybrid modified harmony search and sine cosine algorithm (MHS-SCA) optimized extreme learning machine (ELM) is proposed for brain tumor detection and classification. The IFF-FLICM algorithm is utilized to accurately segment the brain’s magnetic resonance (MR) images to identify the tumor regions. The Mexican hat wavelet transform is employed for feature extraction from the segmented images. The extracted features from the segmented regions are fed into the MHS-SCA-ELM classifier for classification. The MHS-SCA is proposed to optimize the weights of the ELM model to improve the classification performance. Five distinct multimodal and unimodal benchmark functions are considered for optimization to demonstrate the robustness of the proposed MHS-SCA optimization technique. The image Dataset-255 is considered for this study. The quality measures such as SSIM and PSNR are considered for segmentation. The proposed IFF-FLICM segmentation achieved a peak signal-to-noise ratio (PSNR) of 37.24 dB and a structural similarity index (SSIM) of 0.9823. The proposed MHS-SCA-based ELM model achieved a sensitivity, specificity, and accuracy of 98.78%, 99.23%, and 99.12%. The classification performance results of the proposed MHS-SCA-ELM model are compared with MHS-ELM, SCA-ELM, and PSO-ELM models, and the comparison results are presented.

Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942–2019

Introduction Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. Materials and methods Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. Results Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. Conclusions This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

DIPG-55. DIRECT BRAIN-TO-BRAIN WORKFLOW ENABLES THE PRECLINICAL MODELING OF PEDIATRIC GLIOMAS

Abstract Pediatric high-grade gliomas (pHGG) are one of the leading causes of brain cancer deaths in children. Progress towards the characterization of molecular and genetic features in adult high-grade gliomas and subsequent therapies has not yielded similar results in pHGG patients. pHGGs do not readily establish in culture and there has also been a lack of preclinical models to identify new therapeutic targets. Here, we employ a direct brain-to-brain workflow enabling the establishment of rare pediatric tumors including Atypical Teratoid/Rhabdoid Tumor (ATRT), H3_K27ALT diffuse midline gliomas, and H3_G34MUT diffuse hemispheric xenograft models. These Direct, Patient-Derived Orthotopic Xenografts (DPDOX) models recapitulate the clinical, genomic, and transcriptomic landscape of that of the parental tumors. Moreover, we have incorporated each tumor with a secreted gaussia luciferase reporter enabling the minimally-invasive tracking of intracranial tumor burden over time in response to drug perturbations. Taken together, we present a novel approach to establish pHGG models and evaluate new therapeutics.

CTIM-27. PHASE I/II STUDY OF CONTROLLED IL-12 AS IMMUNOTHERAPY FOR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Abstract DIPG, which is the leading cause of pediatric brain cancer death with no effective treatment, has neither a highly immunosuppressive nor inflammatory tumor microenvironment (TME). Therefore, eliciting a pro-inflammatory TME may provide therapeutic benefit. We previously demonstrated in adults with recurrent glioblastoma that loco-regional delivery of interleukin 12 administered under the control of the proprietary transcriptional switch RheoSwitch Therapeutic Systemâ (RTSâ) delivered via a replication-incompetent adenovirus (“Controlled IL-12”) turned “cold” tumors “hot” for up to 5.8 months (Sci Transl Med. 2019;11(505)) and seemed to improve median overall survival as compared with historical controls (SNO 2020). A multicenter, phase I/II, open-label study (NCT03330197) is determining the safety and tolerability of Ad (2 x 1011 viral particles) administered by stereotactic intratumoral injection (Day 0) and 14 daily (Days 1 to 14) V doses (10 or 20 mg, body surface area adjusted). The first DIPG subject enrolled was in April 2020 with completion of the first cohort (arm 1, n=3) enrollment anticipated by September 2020. The first subject has tolerated treatment well with no SAEs during the evaluation period. Endogenous serum cytokines increased (including IFN-g 11.4 pg/mL, Day 3), consistent with V crossing the blood-brain barrier and activating the RTSâ switch to conditionally produce recombinant IL-12. Other biomarkers include plasma PK and circulating DNA. Follow-up is ongoing and enrollment is proceeding. Since development of effective immunotherapy for DIPG likely depends on eliciting a tumor-specific effector immune response, Controlled IL-12 is a promising immunotherapy candidate. The first DIPG subject shows encouraging data on safety, tolerability, serum cytokines and early signs consistent with a clinical response. After completion of dose-escalation, the study may be expanded up to 30 patients, which will be considered the phase II component of the study.

THE ASSOCIATION BETWEEN MOBILE PHONES AND THE RISK OF BRAIN CANCER MORTALITY: A 25‐YEAR CROSS‐COUNTRY ANALYSIS

We investigate the relationship between cell phones and brain cancer using brain cancer death rates for 88 countries between 1990 and 2015 from the World Health Organization and country‐level mobile phone subscription rates from the World Bank. We estimate difference‐in‐difference models including country and year fixed effects and time‐varying country covariates. We find that mobile phone subscription rates are positively and statistically significantly associated with death rates from brain cancer 15–20 years later. In falsification tests, we find few positive associations between mobile phone subscription rates and deaths from rectal, pancreatic, stomach, breast or lung cancer or ischemic heart disease. Finally, differential effects models suggest that mobile phone subscription rates are associated with brain cancer deaths 15–19 years later relative to deaths from other causes. (JEL I15, O33)

RBTT-06. TESSA JOWELL BRAIN MATRIX STUDY: A BRITISH FEASIBILITY STUDY OF MOLECULAR STRATIFICATION AND TARGETED THERAPY TO OPTIMIZE THE CLINICAL MANAGEMENT OF PATIENTS WITH GLIOMA

Abstract In 2016 there were 5250 brain cancer deaths in the UK. Standard treatment is surgical resection followed by chemo-radiotherapy. In most cases of diffuse glioma, complete tumour resection is not feasible. Many chemotherapy drugs have untested penetration through the blood brain barrier, potentially leading to sub-therapeutic concentrations in the tumour. There is need to refine current treatment strategies in relation to the understanding of tumour biology, and rapidly introduce and evaluate novel therapeutic approaches and agents through delivering rigorous clinical trials. The TESSA JOWELL BRAIN MATRIX Study will evaluate the feasibility of delivering precision medicine for brain cancer patients within the NHS. A multicentre, platform feasibility study of 1200 patients with diffuse glioma will build on the 100,000 genome project to develop and evaluate an infrastructure to collect and integrate: 1) real time comprehensive integrated molecular analysis, including whole genome sequencing and epigenetic classification; 2) serial sampling and annotation of tumours; 3) collection of matched clinical data; 4) assessment of patient quality of life; 5) centralised radiological review and response assessment as per RANO criteria. Once developed this will allow rapid introduction of therapeutic trials to specific patient groups. Secondary objectives include: understanding the association between extent of resection and molecular stratification to refine the role of surgery; optimisation and harmonisation of protocols to best collect, manage and store tissue, clinical data, and radiological images in order to provide a resource for researchers, both within and outside of the study. Improve patient recruitment by identifying and removing recruitment barriers and improve the information and consent processes for patients. Promote the development of a national network with expertise in brain cancer. Enrolment of the first patient is expected in late 2019. For further information, please contact the Brain Matrix Trial Office BrainMatrix@trials.bham.ac.uk.

QuickStats: Brain Cancer Death Rates Among Children and Teens Aged 1-19 Years,* by Sex† and Age Group - United States, 2013-2015.

The death rate for brain cancer, the most common cancer cause of death for children and teens aged 1-19 years, was 24% higher in males (0.73 per 100,000) than females (0.59) aged 1-19 years during 2013-2015. Death rates were higher for males than females for all age groups, but the difference did not reach statistical significance for the age group 5-9 years. Death rates caused by brain cancer were highest at ages 5-9 years (0.98 for males and 0.85 for females).

Cell Phones and the Risk of Brain Cancer Mortality: A Twenty-Five Year Cross-Country Analysis

Background: Research into the connection between cellphones and brain cancer faces several difficulties, including recall bias, accounting for confounding factors, and attempting to identify effects that may only be detectable over multiple decades. Methods: We use data on country-level brain cancer death rates between 1990 and 2012 from the World Health Organization and lagged country-level mobile phone subscription rates from the World Bank to investigate the association between cell phones and brain cancer. We use a measure of mobile phone use that is not subject to recall problems, include controls for other country-level characteristics that may influence the prevalence of brain cancer and its mortality rate and identify effects that may only be detectable in the aggregate and over a period of multiple decades.Results: Mobile phone subscription rates are positively associated with death rates from brain cancer 15 years later [pConclusions: Mobile phone use may be associated with increased risk of brain cancer deaths.Impact: As new data become available, it will be possible to use our methods to connect recent variation in mobile phone use with lagged brain cancer mortality. To err on the side of caution, individuals may want to make greater use of the speaker phone and/or texting options on their cell phones or investigate cell phone cases that may deflect radiation away from their ears.

Brain Cancer in Workers Employed at a Laboratory Research Facility.

BackgroundAn earlier study of research facility workers found more brain cancer deaths than expected, but no workplace exposures were implicated.MethodsAdding four additional years of vital-status follow-up, we reassessed the risk of death from brain cancer in the same workforce, including 5,284 workers employed between 1963, when the facility opened, and 2007. We compared the work histories of the brain cancer decedents in relationship to when they died and their ages at death.ResultsAs in most other studies of laboratory and research workers, we found low rates of total mortality, total cancers, accidents, suicides, and chronic conditions such as heart disease and diabetes. We found no new brain cancer deaths in the four years of additional follow-up. Our best estimate of the brain cancer standardized mortality ratio (SMR) was 1.32 (95% confidence interval [95% CI] 0.66–2.37), but the SMR might have been as high as 1.69. Deaths from benign brain tumors and other non-malignant diseases of the nervous system were at or below expected levels.ConclusionWith the addition of four more years of follow-up and in the absence of any new brain cancers, the updated estimate of the risk of brain cancer death is smaller than in the original study. There was no consistent pattern among the work histories of decedents that indicated a common causative exposure.

Colorectal cancer prevention by an optimized colonoscopy protocol in routine practice.

We conducted a retrospective cohort study to investigate the colorectal cancer (CRC) incidence and mortality prevention achievable in clinical practice with an optimized colonoscopy protocol targeting near-complete polyp clearance. The protocol consisted of: (i) telephonic reinforcement of bowel preparation instructions; (ii) active inspection for polyps throughout insertion and circumferential withdrawal; and (iii) timely updating of the protocol and documentation to incorporate the latest guidelines. Of 17,312 patients provided screening colonoscopies by 59 endoscopists in South Carolina, USA from September 2001 through December 2008, 997 were excluded using accepted exclusion criteria. Data on 16,315 patients were merged with the South Carolina Central Cancer Registry and Vital Records Registry data from January 1996 to December 2009 to identify incident CRC cases and deaths, incident lung cancers and brain cancer deaths (comparison control cancers). The standardized incidence ratios (SIR) and standardized mortality ratios (SMR) relative to South Carolina and US SEER-18 population rates were calculated. Over 78,375 person-years of observation, 18 patients developed CRC versus 104.11 expected for an SIR of 0.17, or 83% CRC protection, the rates being 68% and 91%, respectively among the adenoma- and adenoma-free subgroups (all p < 0.001). Restricting the cohort to ensure minimum 5-year follow-up (mean follow-up 6.64 years) did not change the results. The CRC mortality reduction was 89% (p < 0.001; four CRC deaths vs. 35.95 expected). The lung cancer SIR was 0.96 (p = 0.67), and brain cancer SMR was 0.92 (p = 0.35). Over 80% reduction in CRC incidence and mortality is achievable in routine practice by implementing key colonoscopy principles targeting near-complete polyp clearance.

Reduced Risk of Brain Cancer Mortality from Walking and Running

This study aimed to test prospectively whether exercise is associated with lower brain cancer mortality in 111,266 runners and 42,136 walkers from the National Runners' and Walkers' Health Studies. Hazard ratios and 95% confidence intervals (95% CI) from Cox proportional hazards analyses of mortality versus metabolic equivalent hours per day of exercise (MET-hours per day, where 1 MET = 3.5 mL O2·kg·min, or approximately 1-km run). The National Death Index identified 110 brain cancer deaths during an 11.7-yr average follow-up. Runners and walkers were combined because the brain cancer risk reduction did not differ significantly between MET-hours per day run and MET-hours per day walked (P = 0.66). When adjusted for sex, age, race, education, and cohort effects, the risk for brain cancer mortality was 43.2% lower for those who exercised 1.8 to 3.5 MET·h·d (95% CI = 2.6%-66.8% lower, P = 0.04) and 39.8% lower for those who exercised ≥ 3.6 MET·h·d (95% CI = 0.0%-64.0% lower, P = 0.05) compared with <1.8 MET·h·d at baseline. Pooling the runners and walkers who expended ≥ 1.8 MET·h·d showed a 42.5% lower risk of brain cancer mortality for the entire sample (95% CI: 8.0 to 64.1, P = 0.02) and 40.0% lower risk when three deaths that occurred within 1 yr of the baseline survey were excluded (95% CI = 1.3%-62.4%, P = 0.04). The risk for fatal brain cancer decreased in association with running and walking energy expenditure. Our ability to detect an exercise-brain cancer relationship may relate to the use of cohorts specifically designed to detect exercise-health associations, and the calculation of exercise energy expenditure from kilometers per day walked and run rather than time spent exercising.

A Pilot Case-Cohort Study of Brain Cancer in Poultry and Control Workers

We conducted an exploratory study to investigate which exposures (including poultry oncogenic viruses) are associated with brain cancer in poultry workers. A total of 46,819 workers in poultry and nonpoultry plants from the same union were initially followed for mortality. Brain cancer was observed to be in excess among poultry workers. Here we report on a pilot case-cohort study with cases consisting of 26 (55%) of the 47 brain cancer deaths recorded in the cohort, and controls consisting of a random sample of the cohort (n = 124). Exposure information was obtained from telephone interviews, and brain cancer mortality risk estimated by odds ratios. Increased risk of brain cancer was associated with killing chickens, odds ratio (OR) = 5.8 (95% confidence interval, 1.2–28.3); working in a shell-fish farm, OR = 13.0 (95% CI, 1.9–84.2); and eating uncooked fish, OR = 8.2 (95% CI, 1.8–37.0). Decreased risks were observed for chicken pox illness, OR = 0.2 (95% CI, 0.1–0.6), and measles vaccination, OR = 0.2 (95% CI, 0.1–0.6). Killing chickens, an activity associated with the highest occupational exposure to poultry oncogenic viruses, was associated with brain cancer mortality, as were occupational and dietary shellfish exposures. These findings are novel.

HealthViEWS: Mortality Study of Female US Vietnam Era Veterans, 1965-2010

We conducted a retrospective study among 4,734 women who served in the US military in Vietnam (Vietnam cohort), 2,062 women who served in countries near Vietnam (near-Vietnam cohort), and 5,313 nondeployed US military women (US cohort) to evaluate the associations of mortality outcomes with Vietnam War service. Veterans were identified from military records and followed for 40 years through December 31, 2010. Information on underlying causes of death was obtained from death certificates and the National Death Index. Based on 2,743 deaths, all 3 veteran cohorts had lower mortality risk from all causes combined and from several major causes, such as diabetes mellitus, heart disease, chronic obstructive pulmonary disease, and nervous system disease relative to comparable US women. However, excess deaths from motor vehicle accidents were observed in the Vietnam cohort (standardized mortality ratio = 3.67, 95% confidence interval (CI): 2.30, 5.56) and in the US cohort (standardized mortality ratio = 1.91, 95% CI: 1.02, 3.27). More than two-thirds of women in the study were military nurses. Nurses in the Vietnam cohort had a 2-fold higher risk of pancreatic cancer death (adjusted relative risk = 2.07, 95% CI: 1.00, 4.25) and an almost 5-fold higher risk of brain cancer death compared with nurses in the US cohort (adjusted relative risk = 4.61, 95% CI: 1.27, 16.83). Findings of all-cause and motor vehicle accident deaths among female Vietnam veterans were consistent with patterns of postwar mortality risk among other war veterans.

Brain Cancer in Workers Employed at a Specialty Chemical Research Facility

ABSTRACT This study evaluated unique exposures and their relationship to brain cancer mortality in employees of a specialty chemical research facility. Following an exposure assessment that concerned compounds distinct to this facility, the authors conducted a cohort mortality study of 5,284 workers to assess mortality in reference to the general population and a nested case-control study to evaluate brain cancer risk associated with specific jobs and unique chemical exposures. Four hundred eighty-six deaths, including 14 brain cancer deaths, were identified. Overall mortality was lower than expected. Brain cancer mortality was elevated (standardized mortality ratio [SMR] = 2.02, 95% confidence interval [CI] = 1.11–3.40). Exposures to 5 specific chemical categories were assessed. Exploration of work history and the specific chemical exposures did not explain the brain cancer cases. No clear occupational etiology was identified.

Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality

Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

Parity, age at first birth, and risk of death from brain cancer: a population-based cohort study in Taiwan

BackgroundThis study was undertaken to examine whether there is an association between parity and age at first birth and risk of death from brain cancer.MethodsThe study cohort consisted of 1,292,462 women who had a first and singleton childbirth between Jan. 1, 1978 and Dec. 31, 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) of death from brain cancer associated with parity and age at first birth.ResultsThere were 316 brain cancer deaths during 34,980,246 person-years of follow-up. The mortality rate of brain cancer was 0.90 cases per 100,000 person-years. The adjusted HR was 1.35 (95% CI= 0.91-2.01) for women who gave birth between 21 and 25, 1.61 (95% CI=1.05-2.45) for women who gave birth after 25 years of age, respectively, when compared with women who gave birth less than 20 years. A trend of increasing risk of brain cancer was seen with increasing age at first birth. The adjusted HR were 0.73 (95% CI= 0.53-0.99) for women who had 2 children, and 0.60 (95% CI =0.43-0.83) for women with 3 or more births, respectively, when compared with women who had given birth to only 1 child. There was a significant decreasing trend in the HRs of brain cancer with increasing parity.ConclusionsThis study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of death from brain cancer.

Nitrates in Drinking Water and The Risk of Death from Brain Cancer: Does Hardness in Drinking Water Matter?

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO3-N), Ca, and Mg in drinking water was obtained from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO3-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO3-N exposure level was <0.38 ppm, the adjusted OR (95% CI) for brain cancer occurrence was 1.04 (0.85–1.27) for individuals who resided in municipalities served by drinking water with a NO3-N exposure ≥0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

Update of a cohort mortality study of workers exposed to methylene chloride employed at a plant producing cellulose triacetate film base

To update the mortality experience of employees of a factory that produced cellulose triacetate film base at Brantham in the United Kingdom and generate information on the effects of exposure to methylene chloride, in particular, mortality from cardiovascular disease and cancers of the lung, liver and biliary tract, pancreas and brain. All 1,785 male employees with a record of employment at the film factory in 1946-1988 were followed through 2006, including 1,473 subjects exposed to methylene chloride on average for 9 years at a concentration of 19ppm (8h time-weighted average). A total of 559 deaths occurred during the follow-up period. In the subcohort of workers exposed to methylene chloride, substantially reduced mortalities compared with national and local rates were found for all causes, all cancers, and all the principal cancer sites of interest except for brain cancer. There was a small excess of brain cancer deaths (8 observed and 4.4 expected), but no evidence of an association with exposure to methylene chloride. Lung cancer mortality was significantly reduced in exposed workers, even compared to the low mortality rate in the local population (SMR 55). In contrast, mortality from ischaemic heart disease in exposed workers was slightly increased compared with local rates (SMR 102), but was lower in active employees (SMR 94; local rates), where a direct effect of exposure to methylene chloride should be concentrated. The study provided no indication that employment at the plant, or exposure to methylene chloride, had adversely affected the mortalities of workers.

Premature mortality due to cancer in Japan, 1995 and 2005

To better understand premature mortality due to cancer, we estimated years of life lost (YLL) and average years of life lost (AYLL) due to cancer for the years 1995 and 2005, based on data from the Vital Statistic of Japan. In men, we identified a total of 159,623 cancer deaths in 1995 and 196,603 in 2005. Total YLL were 2,342,560.4 and 2,724,066.0 years, respectively. Averaged for all cancers, people died 14.7 years earlier than life expectancy in 1995 and 13.9 years in 2005. AYLL was longest for brain cancer deaths, at 26.3 years earlier than expected in 1995 and 22.8 years in 2005, followed by leukemia. In women, a total of 103,399 cancer deaths occurred in 1995 and 129,338 in 2005. Total YLL were 1,818,960.4 years in 1995 and 2,160,706.5 years in 2005, corresponding to AYLL for all cancer combined of 17.6 and 16.7 years. The AYLL of brain cancer deaths was also the longest, at 29.4 years in 1995 and 27.8 in 2005, followed by leukemia and female sex-related cancers. Results showed that cancer of the stomach, colorectum, liver and lung were the most frequent cancers in both sexes in both 1995 and 2005 and responsible for a remarkable number of YLL. Further, AYLL was greatest for brain cancer and leukemia in both sexes and for sex-related cancers in women, namely breast, cervix and ovarian cancer.