Dataset Information

Allergies and Childhood Acute Lymphoblastic Leukemia: A Case-Control Study and Meta-analysis.

ABSTRACT: Background: Allergic disease is suspected to play a role in the development of childhood acute lymphoblastic leukemia (ALL). Studies conducted over the last several decades have yielded mixed results.Methods: We examined the association between allergy, a common immune-mediated disorder, and ALL in the California Childhood Leukemia Study (CCLS), a case-control study of 977 children diagnosed with ALL and 1,037 matched controls (1995-2015). History of allergies in the first year of life was obtained from interviews, mainly reported by mothers. Logistic regression analyses were conducted to estimate ORs and 95% confidence intervals (CIs), controlling for birth order, daycare attendance, and mode of delivery. In addition, we conducted meta-analyses with data from the CCLS and 12 published studies and employed a new method to estimate between-study heterogeneity (R_b).Results: Overall, no associations were observed between childhood ALL risk and specific allergy phenotypes or any allergy, as a group. However, having any allergy was associated with an increased risk of ALL among the youngest study participants. In the meta-analysis random-effects models, reduced odds of ALL were associated with hay fever (metaOR = 0.65; 95% CI, 0.47-0.90); however, restricting the analysis to studies that used medical records for assessment of allergy or recently published studies led to null or attenuated results.Conclusions: Overall, our findings do not support a clear association between allergy and childhood ALL.Impact: The degree to which epidemiologic studies can inform the relationship between allergies and risk of childhood ALL is limited by R_b. Cancer Epidemiol Biomarkers Prev; 27(10); 1142-50. ©2018 AACR.

SUBMITTER: Wallace AD

PROVIDER: S-EPMC6628274 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Allergies and Childhood Acute Lymphoblastic Leukemia: A Case-Control Study and Meta-analysis.

Wallace Amelia D AD Francis Stephen S SS Ma Xiomei X McKean-Cowdin Roberta R Selvin Steve S Whitehead Todd P TP Barcellos Lisa F LF Kang Alice Y AY Morimoto Libby L Moore Theodore B TB Wiemels Joseph L JL Metayer Catherine C

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180801 10

<b>Background:</b> Allergic disease is suspected to play a role in the development of childhood acute lymphoblastic leukemia (ALL). Studies conducted over the last several decades have yielded mixed results.<b>Methods:</b> We examined the association between allergy, a common immune-mediated disorder, and ALL in the California Childhood Leukemia Study (CCLS), a case-control study of 977 children diagnosed with ALL and 1,037 matched controls (1995-2015). History of allergies in the first year of ...[more]

PMID: 30068517

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Project description:Relapsed pediatric B-acute lymphoblastic leukemia (B-ALL) remains as the leading cause of cancer death among children. Other than stem cell transplantation and intensified chemotherapy, no other improved treatment strategies have been approved clinically. Gene expression profiling represents a powerful approach to identify potential biomarkers and new therapeutic targets for various diseases including leukemias. However, inadequate sample size in many individual experiments has failed to provide adequate study power to yield translatable findings. With the hope of getting new insights into the biological mechanisms underpinning relapsed ALL and identifying more promising biomarkers or therapeutic targets, we conducted a meta-analysis of gene expression studies involving ALL from 3 separate studies.By using the keywords "acute lymphoblastic leukemia", and "microarray", a total of 280 and 275 microarray datasets were found listed in Gene Expression Omnibus database GEO and ArrayExpress database respectively. Further manual inspection found that only three studies (GSE18497, GSE28460, GSE3910) were focused on gene expression profiling of paired diagnosis-relapsed pediatric B-ALL. These three datasets which comprised of a total of 108 matched diagnosis-relapsed pediatric B-ALL samples were then included for this meta-analysis using RankProd approach.Our analysis identified a total of 1795 upregulated probes which corresponded to 1527 genes (pfp?<?0.01; FC?>?1), and 1493 downregulated probes which corresponded to 1214 genes (pfp?<?0.01; FC?<?1) respectively. S100A8 appeared as the top most overexpressed gene (pfp?<?0.01, FC?=?1.8) and is a potential target for further validation. Based on gene ontology biological process annotation, the upregulated genes were most enriched in cell cycle processes (enrichment score?=?15.3), whilst the downregulated genes were clustered in transcription regulation (enrichment score?=?12.6). Elevated expression of cell cycle regulators (e.g kinesins, AURKA, CDKs) was the key genetic defect implicated in relapsed ALL, and serve as attractive targets for therapeutic intervention.We identified S100A8 as the most overexpressed gene, and the cell cycle pathway as the most promising biomarker and therapeutic target for relapsed childhood B-ALL. The validity of the results warrants further investigation.

Project description:BackgroundUnconventional oil and gas development (UOGD) releases chemicals that have been linked to cancer and childhood leukemia. Studies of UOGD exposure and childhood leukemia are extremely limited.ObjectiveThe objective of this study was to evaluate potential associations between residential proximity to UOGD and risk of acute lymphoblastic leukemia (ALL), the most common form of childhood leukemia, in a large regional sample using UOGD-specific metrics, including a novel metric to represent the water pathway.MethodsWe conducted a registry-based case-control study of 405 children ages 2-7 y diagnosed with ALL in Pennsylvania between 2009-2017, and 2,080 controls matched on birth year. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between residential proximity to UOGD (including a new water pathway-specific proximity metric) and ALL in two exposure windows: a primary window (3 months preconception to 1 y prior to diagnosis/reference date) and a perinatal window (preconception to birth).ResultsChildren with at least one UOG well within 2km of their birth residence during the primary window had 1.98 times the odds of developing ALL in comparison with those with no UOG wells [95% confidence interval (CI): 1.06, 3.69]. Children with at least one vs. no UOG wells within 2km during the perinatal window had 2.80 times the odds of developing ALL (95% CI: 1.11, 7.05). These relationships were slightly attenuated after adjusting for maternal race and socio-economic status [odds ratio (OR) =1.74 (95% CI: 0.93, 3.27) and OR=2.35 (95% CI: 0.93, 5.95)], respectively). The ORs produced by models using the water pathway-specific metric were similar in magnitude to the aggregate metric.DiscussionOur study including a novel UOGD metric found UOGD to be a risk factor for childhood ALL. This work adds to mounting evidence of UOGD's impacts on children's health, providing additional support for limiting UOGD near residences. https://doi.org/10.1289/EHP11092.

Dataset Information

Allergies and Childhood Acute Lymphoblastic Leukemia: A Case-Control Study and Meta-analysis.

Publications

Allergies and Childhood Acute Lymphoblastic Leukemia: A Case-Control Study and Meta-analysis.

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