Association between genetic polymorphisms and biomarkers in styrene-exposed workers

Vodička, Pavel; Souček, Pavel; Tates, A.D.; Dušinská, Maria; Sarmanova, Jana; Zamecnikova, Maria; Vodičková, Ľudmila; Koskinen, Mikko; Zwart, F.A. de; Natarajan, A.T.; Hemminki, Kari

doi:10.1016/s0027-5107(01)00214-7

Cited by 75 publications

(38 citation statements)

References 41 publications

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“…It was found that individuals exposed to styrene carrying alleles predisposing to low and medium EPHX1 activity exhibited higher frequencies of chromosomal aberrations than individuals with highactivity alleles. 33 Similar tendency was observed in individuals exposed to butadiene (unpublished data). Thus, we may speculate that highly lipophillic organic solvents as styrene (partition coefficient for fat:blood is 93.8, for lung:blood is 1.46) 34 may accumulate in breast fat and prolong exposure of this tissue to metabolism-related mutagens.…”

Section: Analysis Of the Distribution Of Combinations Of Polymorphismsupporting

confidence: 76%

“…Expression of EPHX1 in breast tissue was already reported 35 and there is also a considerable amount of data on styrene genotoxicity. 33 The role of oxidative stress should be noted as well. Breast tissues of patients with the suggested high-activity genotype of GSTP1 (*1/*1) contained lower level of 8-hydroxy-2 0 -deoxyguanosine, marker of oxidative DNA damage when compared with patients carrying the low-activity alleles.…”

Section: Analysis Of the Distribution Of Combinations Of Polymorphismmentioning

confidence: 99%

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Breast cancer: role of polymorphisms in biotransformation enzymes

et al. 2004

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We aimed at determining whether any association exists between genetic polymorphisms in epoxide hydrolase (EPHX1), NADPH-quinone oxidoreductase (NQO1), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to breast cancer. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in EPHX1 (exons 3 and 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case -control study comprised of 238 patients with breast cancer and 313 healthy individuals. The distribution of genotypes in exon 6 of NQO1 was significantly different between the control group and breast cancer cases. Age-adjusted odds ratio (OR) for variant genotype NQO1*2/*2 was 3.68 (confidence interval (CI) ¼ 1.41 -9.62, P ¼ 0.008). Association of GSTP1*2/*2 genotype as well as that of low EPHX1 activity deduced by combinations of genotypes in exons 3 and 4 with breast cancer was suggestive, but nonsignificant. Individuals simultaneously lacking GSTM1 and carrying at least one GSTP1 variant allele were at significantly higher risk of breast cancer (OR ¼ 2.03, CI ¼ 1.18 -3.50, P ¼ 0.010). Combinations of either GSTM1null or GSTP1*2 with low activity of EPHX1 presented significant risk of breast cancer (OR ¼ 1.88, CI ¼ 1.00 -3.52, P ¼ 0.049 and OR ¼ 2.40, CI ¼ 1.15 -5.00, P ¼ 0.019, respectively) as well. In conclusion, the results suggest that genetic polymorphisms in biotransformation enzymes may play a significant role in the development of breast cancer.

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Section: Analysis Of the Distribution Of Combinations Of Polymorphismsupporting

confidence: 76%

Section: Analysis Of the Distribution Of Combinations Of Polymorphismmentioning

confidence: 99%

Breast cancer: role of polymorphisms in biotransformation enzymes

et al. 2004

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confidence: 99%

“…Vodicka et al (33) showed that polymorphisms in the 5Ј-flanking region and in the DraI site in intron 6 are significantly correlated with single-strand breaks in DNA. The DraI polymorphism is also correlated with increased risk for lung cancer (33)(34)(35)(36)(37), for breast cancer among premenopausal smokers (38), and for renal carcinoma among Caucasian women (39). The RsaI c2 mutated allele in the 5Ј-flanking region was also associated with adenocarcinoma (40), esophageal cancer in a Chinese population (41), nasopharyngeal carcinoma (42), and oral cancer cases (43).…”

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confidence: 99%

Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models

Bansal

Anandatheerthavarada

Prabu

et al. 2013

Journal of Biological Chemistry

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Background: Induced expression of CYP2E1 is known to enhance alcohol liver toxicity. Results: Novel mutations W23R/W30R and L32N in human CYP2E1 alter mitochondrial and microsomal targeting efficiency. Conclusion: Human variants with altered targeting modulate susceptibility of cells to alcohol. Significance: Carriers of the novel W23R/W30R mutation in CYP2E1 are likely to be more susceptible to alcohol toxicity.

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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]. Two polymorphisms in EPHX1, Tyr113 His in exon 3 (rs1051740) and His139Arg in exon 4 (rs2234922), have been identified to affect enzyme activity.…”

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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Association between genetic polymorphisms and biomarkers in styrene-exposed workers

Cited by 75 publications

References 41 publications

Breast cancer: role of polymorphisms in biotransformation enzymes

Breast cancer: role of polymorphisms in biotransformation enzymes

Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models

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

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