Monique Does

Myelodysplastic syndromes: incidence and survival in the United States.

Myelodysplastic syndromes (MDS) became reportable to the Surveillance, Epidemiology, and End Results (SEER) Program (the United States cancer surveillance program) in 2001. This provided the first opportunity to examine the incidence and survival of patients with MDS in the United States using a large, population‐based database.

Ethnic Difference in Daycare Attendance, Early Infections, and Risk of Childhood Acute Lymphoblastic Leukemia

A role for infectious agents has been proposed in the etiology of childhood acute lymphoblastic leukemia (ALL), particularly for common ALL (c-ALL; ALL diagnosed in children ages 2-5 years and expressing CD10 and CD19 surface antigens). We evaluated the possible etiologic role of daycare attendance (a proxy measure for exposure to infectious agents) and infections during infancy in the Northern California Childhood Leukemia Study. A total of 294 incident ALL cases (ages 1-14 years) and 376 individually matched controls were included in this analysis. In non-Hispanic White children, daycare attendance measured by child-hours was associated with a significantly reduced risk of ALL. Compared with children who did not attend any daycare, the odds ratio (OR) for those who had >5,000 child-hours during infancy was 0.42 [95% confidence interval (95% CI), 0.18-0.99] for ALL and 0.33 (95% CI, 0.11-1.01) for c-ALL. Test for trend is also significant, which supports a dose-response relationship. The magnitude of effect associated with the same number of child-hours was stronger for daycare attendance during infancy than for daycare attendance before diagnosis. In addition, self-reported ear infection during infancy was associated with a significantly reduced risk of c-ALL (OR, 0.32; 95% CI, 0.14-0.74) in non-Hispanic White children. In Hispanic children, no association was observed among daycare attendance, early infections, and risk of childhood ALL or c-ALL. These results offer indirect yet strong support for the infectious disease hypothesis in the etiology of ALL in non-Hispanic White children and highlight an important ethnic difference.

Polybrominated diphenyl ethers in residential dust: sources of variability.

We characterized the sources of variability for polybrominated diphenyl ethers (PBDEs) in residential dust and provided guidance for investigators who plan to use residential dust to assess exposure to PBDEs. We collected repeat dust samples from 292 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 to 2007 and during 2010) using household vacuum cleaners and measured 22 PBDEs using high resolution gas chromatography-high resolution mass spectrometry. Median concentrations for individual PBDEs ranged from <0.1-2500ng per g of dust. For each of eight representative PBDEs, we used a random-effects model to apportion total variance into regional variability (0-11%), intra-regional between-household variability (17-50%), within-household variability over time (38-74%), and within-sample variability (0-23%) and we used a mixed-effects model to identify determinants of PBDE levels. Regional differences in PBDE dust levels were associated with residential characteristics that differed by region, including the presence of furniture with exposed or crumbling foam and the recent installation of carpets in the residence. Intra-regional differences between households were associated with neighborhood urban density, racial and ethnic characteristics, and to a lesser extent, income. For some PBDEs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PBDE exposures in studies of childrens health (e.g., the Northern California Childhood Leukemia Study).

Factors Associated With Residential Mobility in Children With Leukemia: Implications For Assigning Exposures

PURPOSE In epidemiologic studies, neighborhood characteristics are often assigned to individuals based on a single residence despite the fact that people frequently move and, for most cancer outcomes, the relevant time-window of exposure is not known. The authors evaluated residential mobility patterns for a population-based series of childhood leukemia cases enrolled in the Northern California Childhood Leukemia Study. METHODS Complete residential history from 1 year before birth to date of diagnosis was obtained for 380 cases diagnosed between 1995 and 2002. All residences were assigned U.S. Census block group designations using a geographic information system. RESULTS Overall, two-thirds (65.8%) of children had moved between birth and diagnosis, and one-third (34.5%) moved during the first year of life. Approximately 25% of the mothers had moved during the year before the childs birth. Multivariable analysis indicated greater residential mobility to be associated with older age of the child at diagnosis, younger age of the mother at childs birth, and lower household income. Among those who had moved, residential urban/rural status for birth and diagnosis residences changed for about 20% of subjects, and neighborhood socioeconomic status for 35%. CONCLUSIONS These results suggest that neighborhood attribute estimates in health studies should account for patterns of residential mobility. Estimates based on a single residential location at a single point in time may lead to different inferences.

Early life exposure to infections and risk of childhood acute lymphoblastic leukemia.

Evidence from a growing number of studies indicates that exposure to common infections early in life may be protective against childhood acute lymphoblastic leukemia (ALL). We examined the relationship between three measures of early life exposure to infections—daycare attendance, birth order and common childhood infections in infancy—with the risk of ALL in non‐Hispanic white and Hispanic children, two ethnicities that show sociodemographic differences. The analysis included 669 ALL cases (284 non‐Hispanic whites and 385 Hispanics) and 977 controls (458 non‐Hispanic whites and 519 Hispanics) ages 1–14 years enrolled in the Northern California Childhood Leukemia Study (NCCLS). When the three measures were evaluated separately, daycare attendance by the age of 6 months (odds ratio [OR] for each thousand child‐hours of exposure = 0.90, 95% confidence interval [CI]: 0.82–1.00) and birth order (OR for having an older sibling = 0.68, 95% CI: 0.50–0.92) were associated with a reduced risk of ALL among non‐Hispanic white children but not Hispanic children, whereas ear infection before age 6 months was protective in both ethnic groups. When the three measures were assessed simultaneously, the influence of daycare attendance (OR = 0.83, 95% CI: 0.73–0.94) and having an older sibling (OR = 0.59, 95% CI: 0.43–0.83) became stronger for non‐Hispanic white children. In Hispanic children, a strong reduction in risk associated with ear infections persisted (OR = 0.45, 95% CI: 0.25–0.79). Evidence of a protective role for infection‐related exposures early in life is supported by findings in both the non‐Hispanic white and Hispanic populations within the NCCLS.

Polycyclic aromatic hydrocarbons in residential dust: sources of variability.

Background: There is interest in using residential dust to estimate human exposure to environmental contaminants. Objectives: We aimed to characterize the sources of variability for polycyclic aromatic hydrocarbons (PAHs) in residential dust and provide guidance for investigators who plan to use residential dust to assess exposure to PAHs. Methods: We collected repeat dust samples from 293 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 through 2007 and during 2010) using household vacuum cleaners, and measured 12 PAHs using gas chromatography–mass spectrometry. We used a random- and a mixed-effects model for each PAH to apportion observed variance into four components and to identify sources of variability. Results: Median concentrations for individual PAHs ranged from 10 to 190 ng/g of dust. For each PAH, total variance was apportioned into regional variability (1–9%), intraregional between-household variability (24–48%), within-household variability over time (41–57%), and within-sample analytical variability (2–33%). Regional differences in PAH dust levels were associated with estimated ambient air concentrations of PAH. Intraregional differences between households were associated with the residential construction date and the smoking habits of residents. For some PAHs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Within-household differences between sampling rounds were largest when the interval between dust sample collections was at least 6 years in duration. Conclusions: Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects.

Polychlorinated biphenyls in residential dust: sources of variability.

We characterized the variability in concentrations of polychlorinated biphenyls (PCBs) measured in residential dust. Vacuum cleaner samples were collected from 289 homes in the California Childhood Leukemia Study during two sampling rounds from 2001 to 2010 and 15 PCBs were measured by high resolution gas chromatography-mass spectrometry. Median concentrations of the most abundant PCBs (i.e., PCBs 28, 52, 101, 105, 118, 138, 153, and 180) ranged from 1.0-5.8 ng per g of dust in the first sampling round and from 0.8-3.4 ng/g in the second sampling round. For each of these eight PCBs, we used a random-effects model to apportion total variation into regional variability (6-11%), intraregional between-home variability (27-56%), within-home variability over time (18-52%), and within-sample variability (9-16%). In mixed-effects models, differences in PCB concentrations between homes were explained by home age, with older homes having higher PCB levels. Differences in PCB concentrations within homes were explained by decreasing time trends. Estimated half-lives ranged from 5-18 years, indicating that PCBs are removed very slowly from the indoor environment. Our findings suggest that it may be feasible to use residential dust for retrospective assessment of PCB exposures in studies of childrens health.

Potential role of selection bias in the association between childhood leukemia and residential magnetic fields exposure: A population-based assessment

PURPOSE Data from the Northern California Childhood Leukemia Study (NCCLS) were used to assess whether selection bias may explain the association between residential magnetic fields (assessed by wire codes) and childhood leukemia as previously observed in case-control studies. METHODS Wiring codes were calculated for participating cases, n=310; and non-participating cases, n=66; as well as for three control groups: first-choice participating, n=174; first-choice non-participating, n=252; and replacement (non-first choice participating controls), n=220. RESULTS Participating controls tended to be of higher socioeconomic status than non-participating controls, and lower socioeconomic status was related to higher wire-codes. The odds ratio (OR) for developing childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64) when all cases were compared to all first-choice controls (participating and non-participating). The OR for developing childhood leukemia in the high current category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to first-choice participating controls, but no associations were observed when participating cases were compared to non-participating controls (OR=1.06, 95% CI: 0.71, 1.57) or to replacement controls (OR=1.06, 95% CI: 0.71, 1.60). CONCLUSIONS The observed risk estimates vary by type of control group, and no statistically significant association between wire codes and childhood leukemia is observed in the California population participating in the NCCLS.

A task-based assessment of parental occupational exposure to organic solvents and other compounds and the risk of childhood leukemia in California

PURPOSE Data on parental occupational exposures and risk of childhood leukemia lack specificity. Using 19 task-based job modules, we examined the relationship between occupational exposure to organic solvents and other compounds and the risk of leukemia in children. METHODS Latino (48%) and non-Latino (52%) children with acute lymphoblastic leukemia (ALL; n=670), acute myeloid leukemia (AML; n=104), and controls (n=1021) were enrolled in a study in California (2000-2008). Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for socio-demographic factors. RESULTS Among children with non-Latino fathers, none of the exposures evaluated were associated with risks of ALL and AML. In contrast, exposure to any organic solvents in Latino fathers was associated with an increased risk of childhood ALL (OR=1.48; 95% CI: 1.01-2.16); in multivariable analyses, the OR for chlorinated hydrocarbons was 2.28 (95% CI: 0.97-5.37) while the ORs were close to one for aromatic hydrocarbons, glycol ethers, and other hydrocarbon mixtures. We also observed an increased risk of ALL with exposure to combustion exhaust/polycyclic aromatic hydrocarbons (PAHs) (ORs=1.70; 95% CI: 1.16-2.57, and 1.46; 95% CI: 0.94-2.26 with and without adjustment for chlorinated hydrocarbons, respectively). Moderately elevated risks of ALL were seen with exposure to metals, paints, and wood dust, although not statistically significant. An increased risk was reported for asbestos based on small numbers of exposed Latino fathers. No associations were reported between maternal exposures to any exposures and childhood ALL and AML. CONCLUSIONS Our data support associations between paternal occupational exposures to chlorinated hydrocarbons, combustion exhaust, metals, and possibly asbestos and the risk of ALL in the children of Latino fathers only.

Exposure to Electrical Contact Currents and the Risk of Childhood Leukemia

Abstract The objectives of this study were to examine the association between contact current exposure and the risk of childhood leukemia and to investigate the relationship between residential contact currents and magnetic fields. Indoor and outdoor contact voltage and magnetic-field measurements were collected for the diagnosis residence of 245 cases and 269 controls recruited in the Northern California Childhood Leukemia Study (2000–2007). Logistic regression techniques produced odds ratios (OR) adjusted for age, sex, Hispanic ethnicity, mothers race and household income. No statistically significant associations were seen between childhood leukemia and indoor contact voltage level [exposure ≥90th percentile (10.5 mV): OR  =  0.83, 95% confidence interval (CI): 0.45, 1.54], outdoor contact voltage level [exposure ≥90th percentile (291.2 mV): OR  = 0.89, 95% CI: 0.48, 1.63], or indoor magnetic-field levels (>0.20 µT: OR  =  0.76, 95% CI: 0.30, 1.93). Contact voltage was weakly correlated with magnetic field; correlation coefficients were r  =  0.10 (P  =  0.02) for indoor contact voltage and r  =  0.15 (P  =  0.001) for outdoor contact voltage. In conclusion, in this California population, there was no evidence of an association between childhood leukemia and exposure to contact currents or magnetic fields and a weak correlation between measures of contact current and magnetic fields.