Tobacco Smoke Exposure and the Risk of Childhood Acute Lymphoblastic and Myeloid Leukemias by Cytogenetic Subtype

Metayer, Catherine; Zhang, Luoping; Wiemels, Joseph L.; Bartley, Karen; Schiffman, Joshua D.; Ma, Xiaomei; Aldrich, Melinda C.; Chang, Jeffrey S.; Selvin, Steve; Fu, Cecilia; Ducore, Jonathan M.; Smith, Martyn T.; Buffler, Patricia A.

doi:10.1158/1055-9965.epi-13-0350

Cited by 75 publications

(89 citation statements)

References 32 publications

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“…California Childhood Leukemia Study (CCLS) participants 7 with complete data on demographic characteristics, smoking history, methylation, and genotyping data were included in the analyses (n D 736). About 54% of participants had childhood acute lymphoblastic leukemia, 59% were males, and approximately half were Hispanic (additional subject characteristics are reported in Table 1).…”

Section: Resultsmentioning

confidence: 99%

Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates

et al. 2016

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Epigenome-wide DNA methylation association studies have identified highly replicable genomic loci sensitive to maternal smoking during gestation. The role of inter-individual genetic variation in influencing DNA methylation, leading to the possibility of confounding or bias of such associations, has not been assessed. We investigated whether the DNA methylation levels at the top 10 CpG sites previously associated with exposure to maternal smoking during gestation were associated with individual genetic variation at the genome-wide level. Genome-wide association tests between DNA methylation at the top 10 candidate CpG and genome-wide SNPs were performed in 736 case and control participants of the California Childhood Leukemia Study. Three of the strongest maternal-smoking sensitive CpG sites in newborns were significantly associated with SNPs located proximal to each gene: cg18146737 in the GFI1 gene with rs141819830 (P D 8.2£10¡44 ), cg05575921 in the AHRR gene with rs148405299 (P D 5.3£10 ¡10), and cg12803068 in the MYO1G gene with rs61087368 (P D 1.3£10 ¡18). For the GFI1 CpG cg18146737, the underlying genetic variation at rs141819830 confounded the association between maternal smoking and DNA methylation in our data (the regression coefficient changed from ¡0.02 [P D 0.139] to ¡0.03 [P D 0.015] after including the genotype). Our results suggest that further studies using DNA methylation at cg18146737, cg05575921, or cg12803068 that aim to assess exposure to maternal smoking during gestation should include genotype at the corresponding SNP. New methods are required for adequate and routine inclusion of genotypic influence on DNA methylation in epigenome-wide association studies to control for potential confounding.

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Section: Resultsmentioning

confidence: 99%

Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates

et al. 2016

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“…Here, we describe an untargeted metabolomics workflow for the analysis of archived DBS from the California Childhood Leukemia Study (CCLS), a population-based study containing approximately 1,000 childhood leukemia cases and 1,200 matched controls (Metayer et al 2013). We measured small molecules with LC-HRMS in archived DBS from 106 control children in the CCLS.…”

Section: Introductionmentioning

confidence: 99%

An untargeted metabolomics method for archived newborn dried blood spots in epidemiologic studies

et al. 2017

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Introduction For pediatric diseases like childhood leukemia, a short latency period points to in-utero exposures as potentially important risk factors. Untargeted metabolomics of small molecules in archived newborn dried blood spots (DBS) offers an avenue for discovering early-life exposures that contribute to disease risks. Objectives The purpose of this study was to develop a quantitative method for untargeted analysis of archived newborn DBS for use in an epidemiological study (California Childhood Leukemia Study, CCLS). Methods Using experimental DBS from the blood of an adult volunteer, we optimized extraction of small molecules and integrated measurement of potassium as a proxy for blood hematocrit. We then applied this extraction method to 4.7-mm punches from 106 control DBS samples from the CCLS. Sample extracts were analyzed with liquid chromatography high resolution mass spectrometry (LC-HRMS) and an untargeted workflow was used to screen for metabolites that discriminate population characteristics such as sex, ethnicity, and birth weight. Results Thousands of small molecules were measured in extracts of archived DBS. Normalizing for potassium levels removed variability related to varying hematocrit across DBS punches. Of the roughly 1,000 prevalent small molecules that were tested, multivariate linear regression detected significant associations with ethnicity (3 metabolites) and birth weight (15 metabolites) after adjusting for multiple testing. Conclusions This untargeted workflow can be used for analysis of small molecules in archived DBS to discover novel biomarkers, to provide insights into the initiation and progression of diseases, and to provide guidance for disease prevention.

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“…Previous cohort and case-control studies have suggested that cigarette smoking may be involved in the etiology of leukemia in many populations [30,31,32]. Cigarette smoke has also been linked to adult myeloid leukemia.…”

Section: Discussionmentioning

confidence: 99%

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

Zhang¹,

Yang²,

Li³

et al. 2015

Cell Physiol Biochem

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Aim: To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients. Methods: A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated. Several polymorphisms in the human OPN encoding gene have been identified. The OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were determined. Results: We identified that the -443C>T polymorphism was the only one which is closely related to AML. Compared with the -443TT carriers, our data showed that the -443CC genotype carriers were significantly related to a higher risk for AML. The -443CC genotype was also more prevalent in poor response groups than in good response group. The -443CC carriers are more likely to have poor response to AML treatment. Cellular assay indicated that the leukemic cell lines receiving the OPN -443C transfection have a significantly lower apoptosis rate to Ara-C treatment compared to cell lines transfected with -443T. Conclusion: The findings of this study suggest OPN-443C>T gene polymorphism may be sued as a molecular for susceptibility and chemotherapy response of AML.

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Tobacco Smoke Exposure and the Risk of Childhood Acute Lymphoblastic and Myeloid Leukemias by Cytogenetic Subtype

Cited by 75 publications

References 32 publications

Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates

Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates

An untargeted metabolomics method for archived newborn dried blood spots in epidemiologic studies

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

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