Pleural Plaques and the Risk of Lung Cancer in Asbestos-exposed Subjects.

Rationale: Asbestos exposure is associated with a dose-dependent risk of lung cancer. The association between lung cancer and the presence of pleural plaques remains controversial.Objectives: To define the relationship between pleural plaques and lung cancer risk.Methods: Subjects were from two cohorts: 1) crocidolite mine and mill workers and Wittenoom Township residents and 2) a mixed-asbestos-fiber, mixed-occupation group. All subjects underwent annual review since 1990, chest X-ray or low-dose computed tomography scan, and outcome linkage to national cancer and mortality registry data. Cox regression, with adjustment for age (as the underlying matching time variable), was used to estimate hazard ratios (HRs) for lung cancer incidence by sex, tobacco smoking, asbestos exposure, presence of asbestosis, and pleural plaques.Measurements and Main Results: For all 4,240 subjects, mean age at follow up was 65.4 years, 3,486 (82.0%) were male, 1,315 (31.0%) had pleural plaques, and 1,353 (32.0%) had radiographic asbestosis. Overall, 3,042 (71.7%) were ever-smokers with mean tobacco exposure of 33 pack-years. In total, 200 lung cancers were recorded. Risk of lung cancer increased with cumulative exposure to cigarettes, asbestos, and presence of asbestosis. Pleural plaques did not confer any additional lung cancer risk in either cohort (cohort 1: HR, 1.03; 95% confidence interval, 0.64-1.67; P = 0.89; cohort 2: HR, 0.75; 95% confidence interval, 0.45-1.25; P = 0.28).Conclusions: The presence of pleural plaques on radiologic imaging does not confer additional increase in the risk of lung cancer. This result is consistent across two cohorts with differing asbestos fiber exposures and intensity.

Low dose CT detected interstitial lung abnormalities in a population with low asbestos exposure.

BACKGROUND: The use of low dose CT (LDCT) chest is becoming more widespread in occupationally exposed populations. There is a knowledge gap as to heterogeneity in severity and the natural course of asbestosis after low levels of exposure. This study reports the characteristics of LDCT-detected interstitial lung abnormalities (ILA). METHODS: The Asbestos Review Program offers annual LDCT, health assessments, and pulmonary function tests to an asbestos-exposed cohort. Asbestosis was defined using the Helsinki Consensus statement and the presence of ILA defined using a protocol for occupational CT reports. At least two of three pulmonary function tests: forced expiratory volume in 1 s (FEV1 );​ forced vital capacity (FVC); and diffusion capacity for carbon monoxide (DLco) were required for analysis of physiological decline. RESULTS: From 1513 cases, radiological ILA was present in 485 (32%). The cohort was 83.5% male with a median age of 68.3 years and a median (IQR) asbestos exposure of 0.7 (0.09-2.32) fiber/ml-year. A mixed occupation, mixed asbestos fiber cohort comprised the majority of the cohort (65.8%). Of those with ILA, 40 (8.2%) had an FVC decline of ≥10% and 30 (6.2%) had a DLco decline of ≥15% per year. Time since first exposure, increasing tobacco exposure and reported dyspnea were independently associated with the presence of ILA. CONCLUSIONS: In this population with relatively low asbestos exposure, LDCT-detected ILA that fits criteria for asbestosis is common, but physiological decline is not. This mild chronic stable phenotype of asbestos-associated ILA contrasts with the traditionally accepted views that asbestosis requires high exposures.

Predictive value of non-specific bronchial challenge testing for respiratory symptoms and lung function in aluminium smelter workers.

OBJECTIVE: To assess the predictive value of bronchial hyper-responsiveness (BHR) for the subsequent development of respiratory symptoms, airflow limitation and decline in lung function among aluminium smelter workers. METHODS: An inception cohort study of new employees at two Australian aluminium smelters was conducted. Participants completed a modified British Medical Research Council respiratory questionnaire, spirometry and a methacholine bronchial challenge test at baseline and at annual follow-up reviews. BHR was defined as PD20 ≤4000 µg. Poisson and mixed effects models were fitted to respiratory symptoms and lung function (forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC)). RESULTS: Baseline interview and lung function testing were completed by 278 workers, who were followed for a median of 4 years. BHR at baseline, present in 82 workers, was not associated with incident wheeze risk ratio (RR)=1.07 (95% CI 0.74 to 1.55) and cough RR=0.78 (95% CI 0.45, 1.35), but there was some increased risk of chest tightness RR=1.40 (95% CI 0.99, 1.98) after adjustment for age, sex, smoking and atopy. BHR at baseline was associated with lower FEV1 and FVC, although the rate of annual decline in FEV1 or FVC was similar between those with or without BHR. The specificity of BHR was 77% for wheeze, 70% for cough and 77% for chest tightness, but the sensitivity was poor, at 33%, 24% and 39%, respectively. CONCLUSION: Methacholine challenge testing at entry to employment was not sufficiently predictive of later adverse respiratory outcomes, and notwithstanding the study limitations is unlikely to be a useful pre-employment or preplacement screening test in the aluminium smelting industry.

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children.

BACKGROUND: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. METHODS: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. RESULTS: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. CONCLUSION: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children.

Perinatal risk factors associated with skin infection hospitalisation in Western Australian Aboriginal and Non-Aboriginal children.

BACKGROUND: Hospitalisation with skin infection in Western Australian (WA) Aboriginal children is common, with the highest rates in infants and children from remote WA. OBJECTIVE: We aimed to quantify infant, maternal, and sociodemographic risk factors for skin infection hospitalisation in WA children, focussing on Aboriginal children aged <17 years. METHODS: We conducted a retrospective population-based cohort study with linked perinatal and hospitalisation data on WA-born children (1996-2012), of whom 31 348 (6.7%) were Aboriginal. We used Cox regression to calculate adjusted hazard ratios and associated population attributable fractions (PAFs) for perinatal factors attributed to first hospitalisation with skin infection. To identify specific risk factors for early-onset infection, we further restricted the cohort to infants aged <1 year. RESULTS: Overall, 5439 (17.4%) Aboriginal and 6750 (1.5%) non-Aboriginal children were hospitalised at least once with a skin infection. Aboriginal infants aged <1 year had the highest skin infection hospitalisation rate (63.2 per 1000 child-years). The strongest risk factors in Aboriginal children aged <17 years were socio-economic disadvantage, very remote location at birth, and multi-parity (≥3 previous pregnancies) accounting for 24%, 23%, and 15% of skin infection hospitalisations, respectively. Other risk factors included maternal age <20 years, maternal smoking during pregnancy, and low birthweight. CONCLUSIONS: We have quantified the relative influence of perinatal risk factors associated with skin infection hospitalisations in WA children, providing measures indicating which factors have the potential to reduce the most hospitalisations. Our evidence not only supports existing calls for substantial government investment in addressing underlying social and environmental barriers to healthy skin in WA Aboriginal children but also identifies potential areas to target health promotion messaging at individuals/families on maternal smoking during pregnancy and skin hygiene for families.

Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom.

OBJECTIVES: The presence of asbestos in public buildings is a legacy of past asbestos use in many developed countries. Of particular concern is the amount and current condition in schools and the vulnerability of children to mesothelioma. Our aim was to compare the risk of mesothelioma between those exposed to blue asbestos as children and as adults at Wittenoom. METHODS: Public sources were used to establish the Wittenoom residents' cohort. Mesothelioma incidence rates per 100 000 person-years at risk were derived for those first exposed to asbestos at Wittenoom as children (<15 years) or adults separately. Proportional hazards survival models examined the slope of the exposure-response relationship between asbestos exposure and incidence of mesothelioma in different sex and age groups. RESULTS: The mesothelioma rate was lower among those first exposed as children (76.8 per 100 000) than those first exposed as adults (121.3 per 100 000). Adjusting for cumulative exposure to asbestos and sex, those exposed as adults had a greater risk of mesothelioma (adjusted HR 2.5, 95% CI 1.7 to 3.7). The slope of the exposure-response relationship did not differ between those exposed as children and those exposed as adults. CONCLUSION: We found no greater susceptibility to mesothelioma among those first exposed to asbestos as children than those first exposed as adults. However, given the long latency of mesothelioma, and the greater years of life yet to be lived by the Wittenoom children, it is likely that there will be more cases of mesothelioma in the future among those first exposed as children.

Migration and work in postwar Australia: mortality profile comparisons between Australian and Italian workers exposed to blue asbestos at Wittenoom.

OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom. METHODS: A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers. RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL). CONCLUSIONS: A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers. IMPACT: Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.

Vitamin D over the first decade and susceptibility to childhood allergy and asthma.

BACKGROUND: Vitamin D (25(OH)D) deficiency has been implicated as a possible risk factor for asthma development, but studies at selected time points measuring 25(OH)D levels during childhood have yielded conflicting findings. Prospective studies tracking 25(OH)D levels during the initiation phase of asthma in early childhood have not been reported. OBJECTIVE: We sought to elucidate relationships between 25(OH)D levels from birth to age 10 years and susceptibility to allergic sensitization, respiratory tract infections, and asthma. METHODS: Asthma-, allergy-, and respiratory tract infection-associated phenotypes (including pathogen identification) were characterized in a high-risk birth cohort. Plasma 25(OH)D concentrations were quantified at birth and at clinical follow-ups at the ages of 0.5, 1, 2, 3, 4, 5, and 10 years, and relationships with clinical outcomes were examined. RESULTS: Cross-sectional analyses demonstrated inverse associations between 25(OH)D concentrations and the risk for concurrent sensitization at age 0.5, 2, and 3 years, and mixed-effects regression demonstrated inverse longitudinal associations of 25(OH)D levels with both sensitization and eczema. Multivariate regression modeling suggested that the number of 25(OH)D-deficient follow-ups was positively associated with risk for asthma/wheeze, eczema, and sensitization at 10 years; adjustment for sensitization (particularly by 2 years) in the asthma/wheeze models reduced 25(OH)D associations with these latter outcomes. 25(OH)D levels were also inversely associated with early nasopharyngeal colonization with Streptococcus species and age of first febrile lower respiratory illness, both of which are known asthma risk factors. CONCLUSION: 25(OH)D deficiency in early childhood is associated with increased risk for persistent asthma, potentially through modulating susceptibility to early allergic sensitization, upper respiratory tract colonization with bacterial pathogens, or both. These relationships are only evident if 25(OH)D status is monitored prospectively and longitudinally.

School performance in children with type 1 diabetes: a contemporary population-based study.

AIMS: Our aim was to examine the school performance of children with type 1 diabetes in comparison to their peers, exploring changes over time, and the impact of clinical factors on school performance. METHODS: The study included data on 666 children with type 1 diabetes from the Western Australia Children's Diabetes Database. (WACDD), a population-based registry, and 3260 school and school year matched non-diabetic children. Records from the National Assessment Program - Literacy and Numeracy (NAPLAN) (2008-2011), which examines four educational outcome domains and is administered annually to all years 3, 5, 7, and 9 children in Australia, were sourced for both groups. Clinical data were obtained for the children with diabetes from the WACDD. RESULTS: No significant difference was observed between those with type 1 diabetes and their peers, across any of the tested domains and school years analysed. No decline over time was observed, and no decline following diagnosis was observed. Type 1 diabetes was associated with decreased school attendance, 3% fewer days attended per year. Poorer glycaemic control [higher haemoglobin A1c (HbA1c)] was associated with a lower test score [0.2-0.3 SD per 1% (10.9 mmol/mol) increase in HbA1c], and with poorer attendance [1.8% decrease per 1% (10.9 mmol/mol) increase in HbA1c]. No association was observed with history of severe hypoglycaemia, diabetic ketoacidosis or age of onset and school test scores. CONCLUSION: These results suggest that type 1 diabetes is not associated with a significant decrement in school performance, as assessed by NAPLAN. The association of poorer glycaemic control with poorer school performance serves as further evidence for clinicians to focus on improving glycaemic control.

Childhood folate, B6, B12, and food group intake and the risk of childhood brain tumors: results from an Australian case-control study.

PURPOSE: The etiology of childhood brain tumors (CBT) is poorly understood, but dietary factors could be involved. In this case-control study of CBT, the possible associations of childhood intake of dietary and supplemental folate, vitamin B6, and vitamin B12 with the risk of CBT were investigated, along with various food groups. METHODS: Cases diagnosed between 2005 and 2010 were identified from 10 pediatric oncology centers in Australia and controls by nationwide random-digit dialling. For study children of ages 3-14 years, diet in the year before diagnosis (or recruitment) was assessed using food frequency questionnaires. Folate intake was adjusted for bioavailability, and dietary micronutrient intake was energy-adjusted. Micronutrients and food groups were analyzed using logistic regression adjusting for relevant confounders. Principal components analysis was conducted to assess food group intake patterns for analysis. RESULTS: Food and micronutrient data were available for 216 cases and 523 controls. Folate intake was associated with a reduced risk of CBT overall (odds ratio for highest tertile vs. lowest: 0.63, 95% confidence interval 0.41, 0.97) and particularly low-grade gliomas (odds ratio for highest tertile vs. lowest: 0.52, 95% confidence interval 0.29, 0.92). Vitamin B6 and B12 intake was not associated with CBT risk, nor was processed meat. CONCLUSIONS: High folate intake during childhood may reduce the risk of CBT. This potentially important finding needs to be corroborated in other studies. If replicated, these results could have important implications for public health recommendations regarding diet during childhood.

Risk of cancer among children with birth defects: a novel approach.

BACKGROUND: Associations between birth defects (BDs) and childhood cancers have been studied previously and have identified several specific birth defect-cancer associations. No studies have examined the risk after exclusion of known associations. METHODS: We analyzed data from high-quality population-based registers of BDs and cancers for Western Australian births 1982 to 2007. The cohort comprised 641,036 babies still alive at 90 days. Two experts independently reviewed all 120 births with a BD and a cancer to determine whether the cancer was congenital, caused by the BD, known to be associated with the BD or otherwise. These categories were used in sensitivity analyses. Cox regression was used to estimate hazard ratios (HRs) for any cancer and specific cancers associated with any BD and specific BDs. RESULTS: The HR for any cancer among children with any BD was 1.96 (95% confidence interval, 1.59-2.43). The HR for any cancer among children with a BD not known to be related to a cancer (n = 57) was 1.19 (95% confidence interval, 0.91-1.56). The HR for the latter association among children diagnosed with cancer before 5 years of age was 1.74 (95% confidence interval, 1.28-2.37). CONCLUSION: This novel approach aimed to prevent inflated HRs arising from reverse causation, and allow identification of associations beyond those already well documented. Larger studies using this method are needed to explore currently undocumented associations between BDs and cancers.

Persistent effects of maternal smoking during pregnancy on lung function and asthma in adolescents.

RATIONALE: The extent to which maternal smoking in pregnancy (MSP) has persisting effects on respiratory health remains uncertain and the mechanisms involved are not fully understood. Alterations in immune function have been proposed as a mechanism contributing to respiratory disease. OBJECTIVES: To determine whether MSP increases risk of respiratory disorders in adolescence and, if so, whether this occurs by decreased lung function, altered immune function, and/or enhanced atopy. METHODS: Data on spirometry, bronchial responsiveness, respiratory symptoms, total and allergen-specific IgE and IgG4, immune function, and inflammatory markers were obtained from 1,129 participants in the 14-year follow-up of the Western Australian Pregnancy (Raine) Cohort and related to MSP using regression analyses. MEASUREMENTS AND MAIN RESULTS: MSP was reported for 21.0% (237 of 1,129) of participants, with 92 (8.1%) reporting current smoking. MSP was associated with some altered immune measures at age 14. MSP was strongly related to reduced lung function in current nonsmokers (forced expiratory flow midexpiratory phase [FEF25-75%], P = 0.016; FEV1/FVC, P = 0.009) and increased risk for current asthma (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.16-2.92; P = 0.01), current wheeze (OR, 1.77; 95% CI, 1.14-2.75; P = 0.011), and exercise-induced wheeze (OR, 2.29; 95% CI, 1.37-3.85; P = 0.002), but not for bronchial hyperresponsiveness or atopy. Adjustment for immune measures and/or lung function in multivariate models did not greatly alter these associations and the increased risks for asthma and wheeze were not modified by sex, atopy, or maternal history of asthma or atopy. CONCLUSIONS: MSP increases risk of asthma and wheezing in adolescence; mechanisms go beyond reducing lung function and exclude altering immune function or enhancing atopy.

Development of a Job-Exposure Matrix (AsbJEM) to Estimate Occupational Exposure to Asbestos in Australia.

INTRODUCTION: Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions. OBJECTIVE: To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data. METHODS: A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation. RESULTS: Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; ≥2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite. CONCLUSION: The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation.

Exposure to household painting and floor treatments, and parental occupational paint exposure and risk of childhood brain tumors: results from an Australian case-control study.

PURPOSE: Childhood brain tumors (CBT) are the leading cause of cancer death in children, yet their etiology remains largely unknown. This study investigated whether household exposure to paints and floor treatments and parental occupational painting were associated with CBT risk in a population-based case-control study conducted between 2005 and 2010. METHODS: Cases were identified through all ten Australian pediatric oncology centers, and controls via nationwide random-digit dialing, frequency matched to cases on age, sex, and state of residence. Data were obtained from parents in mailed questionnaires and telephone interviews. Information on domestic painting and floor treatments, and parental occupational exposure to paint, in key periods relating to the index pregnancy and childhood was obtained for 306 cases and 950 controls. Data were analyzed using unconditional logistic regression, adjusting for frequency matching variables and potential confounders. RESULTS: Overall, we found little evidence that parental, fetal, or childhood exposure to home painting or floor treatments was associated with risk of CBT. There was, though, some evidence of a positive association between childhood exposure to indoor painting and risk of high-grade glioma [odds ratio (OR) 3.31, 95 % confidence interval (CI) 1.29, 8.52] based on very small numbers. The OR for the association between CBT and paternal occupational exposure to paint any time before the pregnancy was 1.32 (95 % CI 0.90, 1.92), which is consistent with the results of other studies. CONCLUSIONS: Overall, we found little evidence of associations between household exposure to paint and the risk of CBT in any of the time periods investigated.

Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and risk of childhood brain tumors.

Childhood brain tumors (CBT) are the second most common childhood cancers, yet their etiology is largely unknown. We investigated whether maternal gestational intake of folate and vitamins B6 and B12 was associated with CBT risk in a nationwide case-control study conducted 2005-2010. Case children 0-14 years were recruited from all 10 Australian pediatric oncology centers. Control children were recruited by national random digit dialing, frequency matched to cases on age, sex, and state of residence. Dietary intake was ascertained using food frequency questionnaires and adjusted for total energy intake. Data from 293 case and 726 control mothers were analyzed using unconditional logistic regression. The odds ratio (OR) for the highest versus lowest tertile of folate intake was 0.70 [95% confidence interval (CI): 0.48, 1.02]. The ORs appeared lower in mothers who drank alcohol during pregnancy (OR = 0.45, 95% CI: 0.22, 0.93), mothers who took folic acid (OR = 0.67, 95% CI: 0.42, 1.06) or B6/B12 supplements (OR = 0.51, 95% CI: 0.25, 1.06) and in children younger than 5 years (OR = 0.50, 95% CI: 0.27, 0.93). These findings are consistent with folate's crucial role in maintenance of genomic integrity and DNA methylation. Dietary intake of B6 and B12 was not associated with risk of CBT.

Ultraviolet radiation exposure and serum vitamin D levels in young children.

AIM: Health benefits of adequate vitamin D levels in the blood include better bone health and a reduced incidence of a range of chronic diseases and infections. Ultraviolet (UV) radiation exposure from the sun is the main source of vitamin D; however, such exposure, especially from a young age, is also a potential risk factor for skin cancer. The current study examined the association of UV exposure with vitamin D production in young children to determine the period of weekly exposure prior to blood testing that affected serum 25-hydroxyvitamin D (25(OH)D) levels. METHODS: Between 2009 and 2011, healthy children aged 3, 6 and 9 years were recruited from the community for a cross-sectional study of nutritional factors and DNA damage. Parents of 464 children provided information on the children's average weekly sun exposure and level of sun protection during each of the 16 weeks before blood sample collection by a domiciliary phlebotomist. RESULTS: Serum 25(OH)D levels were best predicted from UV exposure during the week before blood collection for samples drawn in autumn, summer or spring. For samples drawn in winter, serum 25(OH)D levels were best predicted by UV exposure during the 2 weeks before blood collection. CONCLUSIONS: Consistent weekly sun exposure may be beneficial for young children, especially in winter, to maintain healthy vitamin D levels in the blood. However, confirmation of these results is needed before their public health significance can be fully evaluated.

Parental smoking and risk of childhood brain tumors.

Childhood brain tumors (CBT) are the leading cause of cancer death in children, yet their etiology remains largely unknown. Tobacco smoke contains 61 known carcinogens and increases the risk of several adult cancers. This study investigated associations between parental smoking and risk of CBT in a population-based case-control study conducted between 2005 and 2010. Cases were identified through all ten Australian pediatric oncology centers, controls via nationwide random-digit dialing, frequency matched to cases on age, sex and state of residence. Parental smoking information was obtained for 302 cases and 941 controls through mailed questionnaires that requested average daily cigarette use in each calendar year from age 15 to the child's birth, linked to residential and occupational histories. Data were analyzed using unconditional logistic regression, adjusting for frequency matching variables and potential confounders. Overall, parental smoking before or during pregnancy showed no association with CBT risk. The odds ratios for maternal smoking before and during pregnancy were 0.99 (95% CI: 0.70, 1.40) and 0.89 (95% CI: 0.61, 1.21), respectively, and those for paternal smoking before and during pregnancy were 0.99 (95% CI: 0.71, 1.38) and 1.04 (95% CI: 0.74, 1.46), respectively. In children under 24 months of age, the odds ratios for maternal smoking preconception and during pregnancy were 5.06 (95% CI 1.35-19.00) and 4.61 (95% CI: 1.08, 19.63), although these results were based on modest numbers. Future studies should investigate the associations between maternal smoking and risk of CBT by the child's age of diagnosis.

Parental alcohol consumption and risk of childhood acute lymphoblastic leukemia and brain tumors.

PURPOSE: Childhood acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and brain tumors (CBTs) are the leading cause of cancer death in children. In our Australian case-control studies of these cancers, we investigated whether parental alcohol consumption before or during pregnancy was associated with risk. METHODS: Cases were identified through the ten Australian pediatric oncology centers, and controls were recruited through national random-digit dialling. Detailed information on alcohol consumption, including beverage type, amount, and timing, was collected from 690 case families (388 ALL and 302 CBT) and 1,396 control families. Data were analyzed using unconditional logistic regression. RESULTS: We found no evidence that maternal alcohol use before or during pregnancy was associated with an increased risk of either cancer; rather, there was evidence of inverse associations, particularly with wine. For both cancers, we observed U-shaped associations with paternal alcohol consumption in the year before the pregnancy, possibly driven by reduced risk at moderate levels of beer and wine intake and increased risk associated with high levels of beer intake. Moderate intake of spirits by fathers was associated with an increased risk of CBT but not ALL. These findings would be strengthened by corroboration in other studies. While the inverse associations with wine may be interesting mechanistically, the public health message remains that maternal alcohol use during pregnancy causes serious disorders in the offspring and should be avoided. CONCLUSIONS: Our findings suggest that men, as well as women, should limit their alcohol intake when planning a pregnancy.

Exposure to pesticides and the risk of childhood brain tumors.

PURPOSE: Previous research has suggested positive associations between parental or childhood exposure to pesticides and risk of childhood brain tumors (CBT). This Australian case-control study of CBT investigated whether exposures to pesticides before pregnancy, during pregnancy and during childhood, were associated with an increased risk. METHODS: Cases were recruited from 10 pediatric oncology centers, and controls by random-digit dialing, frequency matched on age, sex, and State of residence. Exposure data were collected by written questionnaires and telephone interviews. Data were analyzed by unconditional logistic regression. RESULTS: The odds ratios (ORs) for professional pest control treatments in the home in the year before the index pregnancy, during the pregnancy, and after the child's birth were 1.54 (95% confidence interval (CI): 1.07, 2.22), 1.52 (95% CI: 0.99, 2.34) and 1.04 (95% CI: 0.75, 1.43), respectively. ORs for treatments exclusively before pregnancy and during pregnancy were 1.90 (95% CI: 1.08, 3.36) and 1.02 (95% CI: 0.35, 3.00), respectively. The OR for the father being home during the treatment was 1.79 (95% CI: 0.85, 3.80). The OR for paternal occupational exposure in the year before the child's conception was 1.36 (95% CI: 0.66, 2.80). ORs for prenatal home pesticide exposure were elevated for low- and high-grade gliomas; effect estimates for other CBT subtypes varied and lacked precision. CONCLUSIONS: These results suggest that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased CBT risk. It may be advisable for both parents to avoid pesticide exposure during this time.