Maternal smoking during pregnancy, genetic polymorphisms of metabolic enzymes, and childhood acute leukemia: the ESCALE Study (SFCE)

Bonaventure, Audrey; Goujon-Bellec, Stéphanie; Rudant, Jérémie; Orsi, Laurent; Leverger, Guy; Baruchel, André; Bertrand, Yves; Nelken, Brigitte; Pasquet, Marlène; Gautier, Michel; Sirvent, Nicolas; Bordigoni, Pierre; Ducassou, Stéphane; Rialland, Xavier; Zélénika, Diana; Hémon, Denis; Clavel, Jacqueline

doi:10.1007/s10552-011-9882-9

Cited by 38 publications

(35 citation statements)

References 61 publications

(60 reference statements)

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“…In total there were 26 unique SNPs corresponding to 14 unique genes. The genes ABCC1 (rs8187858, FET, P = 0.001 [32], cds-synon), CHST3 (rs4148943, FET, P = 0.002, UTR-3), ABCC4 (rs4148551, FET, P = 0.01, UTR-3), CYP2E1 (rs3813867, FET, P = 0.01 [33,34], nearGene-5), and ALDH3A1 (rs887241, FET, P = 0.01, missense [35]) were among the most significant hits. Of the 14 genes identified, three are from the ABCC family (ABCC1, ABCC4, ABCC6), and two are from the CHST family (CHST3, CHST13).…”

Section: Snp Comparative Analysis Of Gemcitabine Responsementioning

confidence: 99%

Pharmacogenomic characterization of gemcitabine response – a framework for data integration to enable personalized medicine

2014

Pharmacogenetics and Genomics

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Objectives Response to the oncology drug gemcitabine may be variable in part due to genetic differences in the enzymes and transporters responsible for its metabolism and disposition. The aim of our in-silico study was to identify gene variants significantly associated with gemcitabine response that may help to personalize treatment in the clinic.Methods We analyzed two independent data sets: (a) genotype data from NCI-60 cell lines using the Affymetrix DMET 1.0 platform combined with gemcitabine cytotoxicity data in those cell lines, and (b) genome-wide association studies (GWAS) data from 351 pancreatic cancer patients treated on an NCI-sponsored phase III clinical trial. We also performed a subset analysis on the GWAS data set for 135 patients who were given gemcitabine + placebo. Statistical and systems biology analyses were performed on each individual data set to identify biomarkers significantly associated with gemcitabine response.Results Genetic variants in the ABC transporters (ABCC1, ABCC4) and the CYP4 family members CYP4F8 and CYP4F12, CHST3, and PPARD were found to be significant in both the NCI-60 and GWAS data sets. We report significant association between drug response and variants within members of the chondroitin sulfotransferase family (CHST) whose role in gemcitabine response is yet to be delineated.Conclusion Biomarkers identified in this integrative analysis may contribute insights into gemcitabine response variability. As genotype data become more readily available, similar studies can be conducted to gain insights into drug response mechanisms and to facilitate clinical trial design and regulatory reviews.

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Section: Snp Comparative Analysis Of Gemcitabine Responsementioning

confidence: 99%

Pharmacogenomic characterization of gemcitabine response – a framework for data integration to enable personalized medicine

2014

Pharmacogenetics and Genomics

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“…Genetic susceptibility to childhood ALL 9 (rs3813867/rs2031920), is provided by a meta-analysis of four studies showing a strong increased risk (dominant: OR = 1.99, 95 % CI 1.32-3.00), and one of two additional studies reported results in a consistent direction [16,49]. Regarding other phase I metabolism genes previously examined, available evidence has been less consistent for the CYP2D6, CYP3A5, and epoxide hydrolase 1 (EPHX1) genes.…”

Section: Xenobiotic Metabolism and Transportmentioning

confidence: 99%

“…Meta-analyses of two variants in CYP2D6, G1934A (rs3892097) and del2637 (rs35742686) [12], each based on results from three studies, show weak evidence of an association, which is reinforced by inconclusive results in a recent study [50] (Table 2). Statistically significant risk estimates have been reported in both directions for CYP3A5 G6986A (rs776746) [16,[51][52][53] and EPHX1 T339C (rs1051740) [16,49,50,54,55], and four studies evaluating EPHX1 A418G (rs2234922) have shown largely non-significant results [49,50,54,55].…”

Section: Xenobiotic Metabolism and Transportmentioning

confidence: 99%

“…The class of slow acetylator alleles (NAT2*5A-5C, *6A, and *7B) is represented by combinations of polymorphic sites (C282T, rs1041983; T341C, rs1801280; C481T, rs1799929; G590A, rs1799930; A803G, rs1208; and G857A, rs1799931). While previous studies have used slightly varying classifications of acetylation status for NAT2, three studies have reported statistically significant increased ALL risks associated with slow acetylator alleles [49,58,59], and two studies observed elevated but non-significant risk estimates [16,53].…”

Section: Xenobiotic Metabolism and Transportmentioning

confidence: 99%

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Current evidence for an inherited genetic basis of childhood acute lymphoblastic leukemia

et al. 2012

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Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and efforts to understand its etiology has followed a paradigm that common genetic variation in the presence of modifiable environmental factors contribute to disease risk. To date, there are numerous reports of candidate gene association studies suggesting an involvement of genetic loci in childhood ALL risk, but the general lack of consistency in results has underscored the need for careful interpretation and confirmation in additional well-designed studies. Complementary efforts using the genome-wide association study approach have shown indisputable evidence that common low penetrance genetic polymorphisms contribute to childhood ALL risk. However, current calculations show that these established disease loci only explain a portion of the total estimated contribution of common genetic variation on childhood ALL risk. Certain candidate gene loci previously examined likely contribute to this unexplained variation in risk, but the challenge moving forward will be to establish which ones based on the accumulating evidence. In this review, we describe the results of the most recent gene association studies in childhood ALL and discuss options for future efforts to advance this area of research.

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“…Recent studies have suggested that the interaction between these genes and environmental factors may also affect the susceptibility to leukemia [10]- [12]. Microsomal epoxide hydrolase (EPHX1), along with CYP, another family of xenobiotic-metabolizing enzymes, plays an important role in both the detoxification and activation of procarcinogens [13] [14] and is considered to be a protective enzyme [15].…”

Section: Introductionmentioning

confidence: 99%

The EPHX1 rs1051740 Polymorphism Is Associated with Childhood Acute Lymphoblastic Leukemia in a Korean Population

Kim¹,

Kim²,

Li³

et al. 2014

ABB

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Microsomal epoxide hydrolase (EPHX1) is involved in the activation and detoxification of exogenous chemicals. Genetic polymorphisms in EPHX1 have been associated with the development of leukemia. To investigate an association between single-nucleotide polymorphisms (SNPs) of EPHX1 and risk factors for childhood acute lymphoblastic leukemia (ALL) in Korean children, we genotyped two SNPs, Tyr113His (rs1051740) and His139Arg (rs2234922) in 185 childhood ALL cases and 536 healthy controls. Genotyping for these two SNPs was performed by simplex pyrosequencing assay and high-resolution melt analysis, respectively. We found that the Tyr113His genotype was associated with a decreased risk of childhood ALL (odds ratio, OR = 0.64, 95% confidence interval, CI = 0.43 -0.93; p = 0.02). There was no association between His139Arg and the combined genotypes and the risk of childhood ALL. These results suggest that the EPHX1 113TyrHis genotype may protect against leukemogenesis in childhood.

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Maternal smoking during pregnancy, genetic polymorphisms of metabolic enzymes, and childhood acute leukemia: the ESCALE Study (SFCE)

Abstract: The ESCALE study did not evidence the interaction between CYP1A12A/2B and maternal smoking suggested previously. The association with NAT25 and the gene-gene interactions need to be replicated.

Cited by 38 publications

References 61 publications

Pharmacogenomic characterization of gemcitabine response – a framework for data integration to enable personalized medicine

Pharmacogenomic characterization of gemcitabine response – a framework for data integration to enable personalized medicine

Current evidence for an inherited genetic basis of childhood acute lymphoblastic leukemia

The EPHX1 rs1051740 Polymorphism Is Associated with Childhood Acute Lymphoblastic Leukemia in a Korean Population

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Maternal smoking during pregnancy, genetic polymorphisms of metabolic enzymes, and childhood acute leukemia: the ESCALE Study (SFCE)

Abstract: The ESCALE study did not evidence the interaction between CYP1A1*2A/2B and maternal smoking suggested previously. The association with NAT2*5 and the gene-gene interactions need to be replicated.

Cited by 38 publications

References 61 publications

Pharmacogenomic characterization of gemcitabine response – a framework for data integration to enable personalized medicine

Pharmacogenomic characterization of gemcitabine response – a framework for data integration to enable personalized medicine

Current evidence for an inherited genetic basis of childhood acute lymphoblastic leukemia

The EPHX1 rs1051740 Polymorphism Is Associated with Childhood Acute Lymphoblastic Leukemia in a Korean Population

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Abstract: The ESCALE study did not evidence the interaction between CYP1A12A/2B and maternal smoking suggested previously. The association with NAT25 and the gene-gene interactions need to be replicated.