Parental social contact in the work place and the risk of childhood acute lymphoblastic leukaemia.

To study the possible relation between parental social contact through occupation, a marker for a child's risk of infection, and childhood acute lymphoblastic leukaemia (ALL), the parents of 294 children with ALL aged 0-14.9 years and 376 matched controls were interviewed about their jobs after their child's birth up to the age of 3 years. Job titles were assigned to a level of social contact, and an index of occupational social contact months was created using the level and the job duration. Positive interactions between this index and rural residence associated with an increased risk of childhood ALL and common ALL (c-ALL) were observed (interaction P-value=0.02 for both, using tertiles of contact months; interaction P-value=0.05 and 0.02 for ALL and c-ALL, respectively, using continuous contact months); such findings were not observed when job durations were ignored. Our data suggest that duration of parental occupation may be important when examining the association between parental social contact in the workplace and childhood leukaemia.

Proteomic analysis of childhood leukemia.

Childhood acute lymphoblastic and myeloid leukemias are stratified into molecular and cytogenetic subgroups important for prognosis and therapy. Studies have shown that gene expression profiles can discriminate between leukemia subtypes. Thus, proteome analysis similarly holds the potential for characterizing different subtypes of childhood leukemia. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze cell lysates from childhood leukemia cell lines as well as pretreatment leukemic bone marrow derived from childhood leukemia cases. Comparison of the acute myeloid leukemia (AML) cell line, Kasumi, and the biphenotypic myelomonocytic cell line, MV4;11, with the acute lymphoblastic leukemia (ALL) cell lines, 697 and REH, revealed many differentially expressed proteins. In particular, one 8.3 kDa protein has been identified as a C-terminal truncated ubiquitin. Analysis of childhood leukemia bone marrow showed differentially expressed proteins between AML and ALL, including a similar peak at 8.3 kDa, as well as several proteins that differentiate between the ALL t(12;21) and hyperdiploid subtypes. These results demonstrate the potential for proteome analysis to distinguish between various forms of childhood leukemia. Future analyses are warranted to validate these findings and to investigate the role of the C-terminal truncated ubiquitin in the etiology of ALL.

Breastfeeding patterns and risk of childhood acute lymphoblastic leukaemia.

The risk of childhood acute lymphoblastic leukaemia (ALL) was investigated in relation to breastfeeding patterns in the Northern California Childhood Leukaemia Study. Data collected by self-administered and in-person questionnaires from biological mothers of leukaemia cases (age 0-14 years) in the period 1995-2002 were matched to birth certificate controls on date of birth, sex, Hispanic ethnic status, and maternal race. Ever compared to never breastfeeding was not associated with risk of ALL at ages 1-14 years (odds ratio=0.99; 95% CI=0.64-1.55) and ages 2-5 years (OR=1.49; 95% CI=0.83-2.65). Various measures of breastfeeding duration compared to absence of breastfeeding also had no significant effect on risk. Complimentary feeding characteristics such as type of milk/formula used and age started eating solid foods among breastfed children were not associated with ALL risk. This study provides no evidence that breastfeeding affects the occurrence of childhood ALL.

RAS mutation is associated with hyperdiploidy and parental characteristics in pediatric acute lymphoblastic leukemia.

We explored the relationship of RAS gene mutations with epidemiologic and cytogenetic factors in a case series of children with leukemia. Diagnostic bone marrow samples from 191 incident leukemia cases from the Northern California Childhood Leukemia Study were typed for NRAS and KRAS codon 12 and 13 mutations. A total of 38 cases (20%) harbored RAS mutations. Among the 142 B-cell acute lymphoblastic leukemia (ALL) cases, RAS mutations were more common among Hispanic children (P=0.11) or children born to mothers <30 years (P=0.007). Those with hyperdiploidy at diagnosis (>50 chromosomes) had the highest rates of RAS mutation (P=0.02). A multivariable model confirmed the significant associations between RAS mutation and both maternal age and hyperdiploidy. Interestingly, smoking of the father in the 3 months prior to pregnancy was reported less frequently among hyperdiploid leukemia patients than among those without hyperdiploidy (P=0.02). The data suggest that RAS and high hyperdiploidy may be cooperative genetic events to produce the leukemia subtype; and furthermore, that maternal age and paternal preconception smoking or other factors associated with these parameters are critical in the etiology of subtypes of childhood leukemia.

Daycare attendance and risk of childhood acute lymphoblastic leukaemia.

The relationship between daycare/preschool ("daycare") attendance and the risk of acute lymphoblastic leukaemia was evaluated in the Northern California Childhood Leukaemia Study. Incident cases (age 1-14 years) were rapidly ascertained during 1995-1999. Population-based controls were randomly selected from the California birth registry, individually matched on date of birth, gender, race, Hispanicity, and residence, resulting in a total of 140 case-controls pairs. Fewer cases (n=92, 66%) attended daycare than controls (n=103, 74%). Children who had more total child-hours had a significantly reduced risk of ALL. The odds ratio associated with each thousand child-hours was 0.991 (95% confidence interval (CI): 0.984-0.999), which means that a child with 50 thousand child-hours (who may have, for example, attended a daycare with 15 other children, 25 h per week, for a total duration of 30.65 months) would have an odds ratio of (0.991)(50)=0.64 (95% CI: 0.45, 0.95), compared to children who never attended daycare. Besides, controls started daycare at a younger age, attended daycare for longer duration, remained in daycare for more hours, and were exposed to more children at each daycare. These findings support the hypothesis that delayed exposure to common infections plays an important role in the aetiology of childhood acute lymphoblastic leukaemia, and suggest that extensive contact with other children in a daycare setting is associated with a reduced risk of acute lymphoblastic leukaemia.

Evaluating the health significance of hazardous air pollutants using monitoring data.

OBJECTIVE: Though many contaminants are released into the atmosphere, in the US only six air pollutants-ozone, particulate matter, sulfur dioxide, carbon monoxide, nitrogen dioxide, and lead-are closely monitored and carefully assessed for health significance. Other pollutants, even if highly toxic, are neither widely monitored nor routinely assessed at the national level. The goal of this study was to analyze the availability of information needed to characterize the health significance of hazardous air pollutants, focusing on urban areas in California. METHODS: The authors compared different approaches to identifying which contaminants should be considered hazardous air pollutants of potential health concern; reviewed the availability of toxicity values for these pollutants; and analyzed the usefulness of air monitoring data from California agencies for determining populations risks, by comparing method detection limits with health benchmarks. RESULTS: Approaches to identifying air contaminants of possible health concern differ. Toxicity values are not available for many hazardous air pollutants, including those identified in the Clean Air Act. In California, monitoring data are available for many, though not all, pollutants of concern. Monitoring methods for several pollutants do not have adequate sensitivity to detect all relevant concentrations. CONCLUSION: The information necessary to fully assess the health significance of hazardous air pollutants is not currently available.

Whole genome amplification increases the efficiency and validity of buccal cell genotyping in pediatric populations.

The collection of buccal cells provides a noninvasive method for obtaining DNA for genetic studies. Here we report the results on buccal cell genotyping from our ongoing study of childhood leukemia in Northern California. We have collected buccal samples from children ranging in age from 4 months to 15 years using an interviewer- or nurse-administered protocol using a cytology brush. Initial results of the genotyping, including the glutathione S-transferase mu, glutathione S-transferase theta, NAD(P)H:quinone oxidoreductase, and methylenetetrahydrofolate reductase polymorphisms, were disappointing because many specimens contained little DNA, failed repeated attempts at PCR amplification, and produced unreliable results. Here we evaluate a solution to the problem that involves whole genome amplification using the improved primer extension preamplification methodology. Sixty cases of pediatric acute leukemia were studied; five PCR-based genotypes were attempted using buccal cell DNA and whole genome amplified (WGA) buccal DNA. Results were compared with genotyping results using DNA isolated from peripheral whole blood or bone marrow for each child. The standard buccal protocol failed to yield successful PCR reactions in 30-57% of specimens, whereas WGA-buccal was markedly more efficient (2-5% failed PCR). A success rate of 100% was achieved with one repeat test of the failed WGA-PCR reactions. Misclassification of genotype was common for the glutathione S-transferase theta marker using the standard buccal procedure. The WGA-buccal protocol, however, produced genotyping results fully concordant with the referent blood or bone marrow DNA results for all five loci. DNA yields were increased by WGA to allow for approximately 900 PCR reactions/brush. WGA is very useful for improving the efficiency and validity of PCR-based genotyping in pediatric populations.

Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database.

BACKGROUND: Adenocarcinomas of the oesophagus and proximal stomach are the most rapidly increasing malignancies in some countries; however, there are no comparative studies on global disease incidence, and the relationships between these two malignancies are undefined. METHODS: We evaluated the cumulative rates and age-specific incidence rates per 100 000 population for adenocarcinomas of the oesophagus and proximal stomach for all countries in the Cancer Incidence in Five Continents database, and compared them with rates for oesophageal squamous cell carcinoma. RESULTS: Substantial variations in cumulative cancer rates were found between genders, between countries, between different ethnicities within the same country, and within the same ethnicity residing in different countries. Cumulative rates (ages 0-74 years) for oesophageal adenocarcinoma varied from 0 (e.g. Thailand) to 0.6 (Scotland, males, 95% CI : 0.56, 0.64); for proximal stomach cancer from 0 (Singapore, Malay females, 95% CI : -0.01, 0.11) to 0.52 (The Netherlands, males, 95% CI : 0.49, 0.55); and for oesophageal squamous cell carcinomas from 0 (non-Jews in Israel, females) to 1.84 (Brazil, Porto Alegre, males, 95% CI : 1.42, 2.26). There was a continuous increase in age-specific incidence rates with advancing age for oesophageal/proximal stomach adenocarcinomas, but a decrease in age-specific incidence rates for oesophageal squamous cell carcinoma after age 75 years. The cumulative rate trends for adenocarcinomas of the oesophagus and proximal stomach were often dissimilar, and varied by country, gender, and ethnicity. CONCLUSIONS: These results suggest that different risk factors may be associated with adenocarcinomas of the oesophagus versus the proximal stomach; the marked rate variation implies a substantial environmental component to the recent incidence changes.

Mortality and morbidity of workers exposed to acrylonitrile in fiber production.

This study assessed the risk of cancer mortality and incidence among 2559 employees exposed to acrylonitrile in the production of Orlon at 2 plants in 1944-1991. Latency, duration of exposure, highest level of exposure ever experienced, and cumulative exposure were used as indicators of exposure. The average duration of exposure for the workers was 7.6 years with an average cumulative exposure of 57.6 ppm-years. Overall mortality was lower than expected in a comparison with the United States population and all DuPont employees [454 deaths, standardized mortality ratios (SMR) of 69 and 91, respectively)]. All the cancer death ratios were lower than expected in a similar comparison. The SMR values for specific sites did not differ significantly from the expected values. Mortality from all cancers and from prostate, respiratory, and digestive cancer did not show any significantly associated increases or a consistent pattern suggestive of a dose-response. The cancer morbidity patterns were similarly unremarkable.

Disease and injury in California with projections to the year 2007. Implications for medical education.

In this article, as part of an evaluation of the future of medical education in California, we characterize the distribution of disease and injury in California; identify major factors that affect the epidemiology of disease and injury in California, and project the burden of disease and injury for California's population to the year 2007. Our goal is to elucidate the major causes of illness and disability at present and in the near future in order to focus state resources on the interventions likely to have the greatest impact. Data from various governmental agencies were utilized; the base year, 1993, is the most recent year with sufficient information available when this report was prepared. Several major risk factors have decreased, including smoking (30% decline from 1984 to 1993) and drinking and driving. However, hypertension prevalence has not changed, and overweight has increased dramatically. Poverty continues to burden about 15% of Californians, with poverty highest among children. During 1993, 220,271 Californians died, with 3 major causes accounting for 61% of these deaths: coronary heart disease (31%), cancer (23%), and stroke (7%). In terms of potential years of life lost (years lost before age 65), the most important causes of death in 1993 were unintentional injury (756 years lost/100,000 population), cancer (632 years), and the acquired immunodeficiency syndrome (AIDS; 491 years). Mortality rates were highest among blacks and lowest among Asians. Overall mortality in California has been declining for decades; in just 1 decade, from 1980 to 1991, mortality declined from 780 to 680 deaths per 100,000 population. Several major causes of death have declined, including coronary heart disease, stroke, unintentional injury, cirrhosis, and suicide, while others have increased, for example, chronic obstructive lung disease and diabetes mellitus. Death from AIDS increased dramatically in the past decade, but is leveling off, and death from cancer is beginning to decline. Rates for overall mortality and morbidity, and for most specific conditions, should continue to decline. A projected 28% population increase by 2007 will yield a corresponding increase in the absolute level of disease cases and death; a disproportionate increase in younger and older groups will yield increased conditions affecting young (unintentional injury, AIDS) and older (heart disease, cancer, stroke, diabetes mellitus) people. Californians should experience overall improved health in coming years, reaping benefits of reduced environmental and behavioral risk factors as well as improved medical treatment and rehabilitation. Coordinated strategies for health promotion, disease prevention, delivery of medical treatment, and rehabilitation are needed to maintain and improve present levels of health across the life span.

Maternal residential proximity to hazardous waste sites and risk for selected congenital malformations.

Using data from two population-based case-control studies, we investigated whether maternal residential proximity to hazardous waste sites increased the risk for neural tube defects, conotruncal heart defects, and oral cleft defects in California. We obtained a residential history by interview for mothers of 507 neural tube defect cases (82.7% of eligible) and their 517 controls (84.6%); and 201 heart cases (84.4%), 439 cleft cases (82.2%), and their 455 controls (72.1%). We identified the locations of 764 inactive hazardous waste sites and systematically collected information on site-related contamination for the subset of 105 National Priority List sites. After controlling for several potential confounders, we found little or no increased risk for maternal residence in a census tract containing a site [odds ratio (OR) = 0.9, 95% confidence interval (CI) = 0.7-1.3 for neural tube defects; OR = 1.3, 95% CI = 0.8-2.1 for heart cases; OR = 1.2, 95% CI = 0.8-1.8 for clefts], but elevated risks for neural tube defects (OR = 2.1, 95% CI = 0.6-7.6) and heart defects (OR = 4.2, 95% CI = 0.7-26.5) for maternal residence within 1/4 mile of a National Priority List site. Furthermore, we observed elevated ORs (> or = 2.0) for neural tube defects and heart defects in association with maternal residence within 1 mile of National Priority List sites containing selected chemical contaminants. Among controls, only 0.6% and 4.4% lived within 1/4 mile and 1 mile of a National Priority List site, respectively, resulting in imprecision in risk estimation.

Occupational electric and magnetic field exposure and leukemia. A meta-analysis.

We conducted a meta-analysis to acquire an understanding of the association between leukemia and occupational exposure to electric and magnetic fields. To explore sources of heterogeneity, study characteristics were scored and examined using regression analysis. While most studies present a small elevation in risk, the apparent lack of a clear pattern of exposure to EMF and risk of leukemia substantially detracts from the hypothesis that measured magnetic fields in the work environment are responsible for the observed excess risk of leukemia. Findings were not sensitive to assumptions, influence of individual studies, weighting schemes, and modeling. Some evidence of publication bias is noted.

Regulatory reform proposals and the public health.

The U.S. Congress is considering legislation that would change policy for environmental health in important ways. Current approaches have been criticized for addressing the wrong set of priorities and consuming too many resources. The legislation requires additional analyses and sets new decision criteria to be applied to federal agency actions taken to protect the environment and public health. Close review of the legislation suggests that though it is intended to address identified problems, it is unlikely to lead to an improved basis for public policy and is likely to paralyze the regulatory process. Reform proposals that reduce rather than increase fragmentation of decision-making and that address problems comprehensively rather than selectively are needed.

Occupational electric and magnetic field exposure and brain cancer: a meta-analysis.

We conducted a meta-analysis to acquire an understanding of the association between central nervous system cancer and occupational exposure to electric and magnetic fields. To explore sources of heterogeneity, study characteristics were scored and examined using regression analysis. An inverse-variance weighted pooling leads to a small overall increase in relative risk (10 to 20%) for the broad group of electrical occupations. One of the largest differences was lower relative risk for Scandinavian studies. Lower relative risks were also reported in cohort- and incidence-based studies. Findings were not sensitive to assumptions, including unpublished data, influence of individual studies, weighting schemes, and modeling. Whereas most studies present a small elevation in risk, there is considerable heterogeneity among the results.