Parental occupational paint exposure and risk of childhood leukemia in the offspring: findings from the Childhood Leukemia International Consortium

Purpose

It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring.

Methods

We obtained individual level data from 13 case–control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression.

Results

Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95 % confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95 % CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95 % CI 0.65, 1.41) and 1.31 (95 % CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest.

Conclusions

Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.     

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.     

Determinants of agricultural pesticide concentrations in carpet dust

Background: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes.Objective: We identified determinants of concentrations of agricultural pesticides in dust.Methods: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California. We measured concentrations of seven pesticides used extensively in agriculture (carbaryl, chlorpyrifos, chlorthal-dimethyl, diazinon, iprodione, phosmet, and simazine). We estimated use of agricultural pesticides near residences from a statewide database alone and by linking the database with crop maps. We calculated the density of pesticide use within 500 and 1,250 m of residences for 180, 365, and 730 days before collection of dust and evaluated relationships between agricultural pesticide use estimates and pesticide concentrations in carpet dust.Results: For five of the seven pesticides evaluated, residences with use of agricultural pesticides within 1,250 m during the previous 365 days had significantly higher concentrations of pesticides than did residences with no nearby use. The highest correlation with concentrations of pesticides was generally for use reported within 1,250 m of the residence and 730 days before sample collection. Regression models that also accounted for occupational and home use of pesticides explained only a modest amount of the variability in pesticide concentrations (4–28%).Conclusions: Agricultural pesticide use near residences was a significant determinant of concentrations of pesticides in carpet dust for five of seven pesticides evaluated.     

Fetal growth and body size genes and risk of childhood acute lymphoblastic leukemia

Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL) may be initiated in utero or early in the postnatal period. High birth weight (or rapid fetal growth) is associated with risk of ALL, but the mechanisms are not understood. In a population-based epidemiologic study of childhood ALL, we utilized a haplotype-based approach to assess the role of eight genes involved in fetal growth and body size regulation in 377 childhood ALL cases and 448 controls. We found significant haplotype associations with risk of childhood ALL for IGF1 among non-Hispanics and Hispanics together (p?=?0.002), for IGF2 among Hispanics (p?=?0.040), and for IGF2R among Hispanics and non-Hispanics (p?=?0.051 and 0.009, respectively). No haplotype associations were observed for IGF1R or the studied genes involved in body size regulation, including LEP, LEPR, GHRL, and NPY. Our study is the first to identify an association between the genes involved in the IGF axis and risk of childhood ALL. These findings for childhood ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are not yet fully differentiated and therefore more susceptible to malignant transformation. Additional studies are needed to confirm these findings and identify specific causal variants.     

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.     

Recruitment of New Immigrants Into a Randomized Controlled Prevention Trial: The <Emphasis Type="Italic">Live Well</Emphasis> Experience

Minority populations are hard to reach with prevention interventions because of cultural and logistical barriers to recruitment. Understanding how to overcome these barriers is pertinent to reducing the elevated burden of obesity within these underserved communities. To inform this literature gap, we explore the processes and outcomes of recruitment for Live Well—a randomized controlled obesity prevention intervention targeting new immigrant mothers and children from Brazil, Latin America, and Haiti who were residing in the greater Somerville, MA area. We employed community-based participatory research principles to develop and implement five culturally-adapted recruitment activities (posters and flyers, media announcements, church outreach, participant referrals, and community organization partnerships) and tracked enrollment for the total and stratified samples of 406 dyads (37% Brazilian, 29% Latino, 33% Haitian). We describe how strategic partnerships were built and sustained within the intervention community, and detail the key adjustments that contributed to our success. Ultimately, community organization partnerships and participant referrals enrolled a collective majority of participants (34% and 25%, respectively); however, stratified analyses revealed variation by ethnicity: Haitian immigrants responded best to ethnic-based media announcements (44%), whereas Latino and Brazilian immigrants were most responsive to community organization outreach (45% and 38%, respectively). Implications from our findings enhance the literature on recruiting hard-to-reach communities into prevention research: some less integrated communities may respond more to grassroots activities with direct engagement, whereas communities with more social capital may be more responsive to top-down, community-wide collaborations. Furthermore, we suggest that strategic and trusting partnerships are key facilitators of recruitment, and future researchers must understand communities’ culture and social networks when building relationships. Our analyses provide rare insight into best practices to overcome specific cultural barriers to recruitment which future investigators can use to better reach underserved communities with prevention research.     

Hemorrhagic rectocolitis and carcinoma of the colon. Contribution of flow cytometry. Report of 3 cases

Carcinoma complicating ulcerative colitis, although an uncommon event, is well known but follow-up of patients to detect high-grade dysplasia as a potential indicator for colectomy is very difficult. Retrospective morphological and cytometrical analysis of three resected colons harboring carcinoma coming from patients with ulcerative colitis were performed. It allowed to confirm the value of this technique. Histogram patterns varied between narrow unimodal in quiescent mucosa to broad unimodal with high IP (proliferation index) in regenerative mucosa and aneuploid in high dysplasic mucosa and carcinoma. In addition to histopathology and in spite of a patchy distribution of aneuploidy, different degrees of dysplasia in mucosa and technical sensibility DNA (desoxyribonucleic acid) analysis in long-standing ulcerative colitis seems to be helpful in the detection of potential malignancy.     

Leptospirosis caused by Leptospira icterohaemorrhagiae of the pseudo-surgical type: a case

The authors report a case of fatal leptospirosis due to Leptospira icterohaemorrhagiae revealed by typical signs of acute cholecystitis and associated with pancreatitis in a 73 year old patient presenting with gallstones. The initial clinical findings were highly suggestive of severe but typical cholecystitis and the final diagnosis was only considered when the patient's condition worsened despite surgery, with increasing obstructive jaundice and multiple organ failure. Pancreatitis was an autopsy finding. Misleading, especially gastrointestinal symptoms are frequent in leptospirosis. Hence an early diagnosis is an essential condition for a successful antibiotic management in severe cases of leptospirosis. This possibility should be considered whenever a patient presents with infectious obstructive jaundice. The patient has to be questioned concerning possible contact with contaminated animals and, when in doubt, the presence of specific antibodies should be investigated.     

Catheter ablation of Mahaim fibers with preservation of atrioventricular nodal conduction

Three patients with refractory preexcited tachycardia implicating Mahaim fibers underwent attempted catheter ablation of the accessory pathway. In the absence of demonstrable retrograde conduction in Mahaim fibers, we located the accessory pathway ventricular insertion site using the criteria of concordance between paced and spontaneous QRS morphologies during pace-mapping and earliest onset of local electrogram relative to surface preexcited QRS. At this site, a QS-like pattern of unfiltered unipolar electrograms with steep downstroke was recorded. The optimal site appeared radiologically at the right ventricular anterior wall or the adjacent septum, 2-4 cm from the tricuspid anulus. Three to six 160-J shocks were delivered at this site using an anterior chest wall plate as anode. After fulguration, conduction through the Mahaim tract was absent. A right bundle branch block persisted in two patients. All patients remained free of preexcited tachycardia during 12-16 months of follow-up. Postablation electrophysiological assessment showed no preexcitation in any patient. No reciprocating tachycardia was inducible, even during isoproterenol infusion. Atrioventricular nodal conduction parameters were unchanged from baseline study. Catheter ablation of Mahaim fibers is an effective alternative method for the treatment of tachycardias that include the accessory pathway in the circuit.