Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Assessment of occupational risks to extremely low frequency magnetic fields: Validation of an empirical non-expert approach.

The expert method of exposure assignment involves relying on chemists or hygienists to estimate occupational exposures using information collected on study subjects. Once the estimation method for a particular contaminant has been made available in the literature, it is not known whether a non-expert, briefly trained by an expert remaining available to answer ad hoc questions, can provide reliable exposure estimates. We explored this issue by comparing estimates of exposure to extremely low frequency magnetic fields (ELF-MF) obtained by an expert to those from a non-expert. Using a published exposure matrix, both the expert and non-expert independently calculated a weekly time-weighted average exposure for 208 maternal jobs by considering three main determinants: the work environment, magnetic field sources, and duration of use or exposure to given sources. Agreement between assessors was tested using the Bland-Altman 95% limits of agreement. The overall mean difference in estimates between the expert and non-expert was 0.004 µT (standard deviation 0.104). The 95% limits of agreement were - 0.20 µT and + 0.21 µT. The work environments and exposure sources were almost always similarly identified but there were differences in estimating exposure duration. This occurred mainly when information collected from study subjects was not sufficiently detailed. Our results suggest that following a short training period and the availability of a clearly described method for estimating exposures, a non-expert can cost-efficiently and reliably assign exposure, at least to ELF-MF.

Strategies for genetic association analyses combining unrelated case-control individuals and family trios.

In genetic association studies, analyses integrating data or estimates from unrelated case-control individuals and case trios (case offspring and their parents) can increase statistical power to identify disease susceptibility loci. Data on control trios may also be available, but how and when their use is advantageous is less familiar and is described here. In addition, the authors examine assumptions and properties of hybrid analyses combining association estimates from unrelated case-control individuals together with case and control family trios, focusing on low-prevalence disease. One such assumption is absence of population stratification bias (PSB), a potential source of confounding in case-control analyses. For detection of PSB, the authors discuss 4 possible tests that assess equality between individual-level and family-based estimates. Furthermore, a weighted framework is presented, in which estimates from analyses combining unrelated individuals and families (most powerful but subject to PSB) and family-based analyses (robust to PSB) are weighted according to the observed PSB test P value. In contrast to existing hybrid designs that combine individuals and families only if no significant PSB is detected, the weighted framework does not require specification of an arbitrary PSB testing level to establish significance. The statistical methods are evaluated using simulations and applied to a candidate gene study of childhood leukemia (Quebec Childhood Leukemia Study, 1980-2000).

Severity of silicosis at compensation between medically screened and unscreened workers.

OBJECTIVE: Most developed countries have medical surveillance programs for some of the workers (typically miners) exposed to silica, but the impact of these programs is not documented. METHODS: Clinical data from 1388 compensated silicotic workers in Quebec, Canada, were used. The severity of disease at compensation was compared between workers in the surveillance program and those who were not. RESULTS: Predicted vital capacity at less than 80% at compensation was less likely among workers under surveillance than among those who were not (odds ratio = 0.59; 95% confidence interval 0.44-0.80); the occurrence of a radiological image with large opacities and profusion of category 1/1 or more was also less likely in the group with surveillance (odds ratio = 0.60; 95% CI = 0.39-0.92). CONCLUSIONS: The data indicate a benefit from medical surveillance but alternative explanations are discussed.

Socioeconomic status and utilization of health care services among asthmatic children.

We evaluated the relation between socioeconomic factors and hospitalization as well as emergency department (ED) visits among asthmatic children who had universal access to health care. Newly diagnosed asthmatic children 3-4 years of age were followed up for a period of 6 years. Information on hospitalization and ED visits was obtained by interviewing parents. Socioeconomic status (SES) was measured by paternal occupation, race, type of dwelling, and an index of crowding. After adjusting for asthma severity, logistic regression analysis showed that children with fathers in the economically least advantaged occupations were more likely to be hospitalized due to their asthma [father's occupation group 3 (FOG3), odds ratio (OR)=2.1, 95% confidence interval (95% CI)=0.2-19.8; father's occupation group 4 (FOG4), OR=13.9, 95% CI=1.1-181.4]. The probability of emergency department visits was not significantly different according to the studied variables. Emergency department visits were not influenced by SES variables, probably due to the absence offinancial barriers to access health care. However, SES differences in hospitalization may suggest differential management and/or treatment practices according to socioeconomic status at the emergency departments.