Lung cancer susceptibility in relation to combined polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase P1

To‐Figueras, Jordi; Gené, M.; Gómez‐Catalán, Jesús; Piqué, Ester; Borrego, N.; Corbella, Jacint Corbella i

doi:10.1016/s0304-3835(01)00626-7

Cited by 49 publications

(33 citation statements)

References 19 publications

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“…Consecutively, a number of case -control studies have examined the influence of the mEH polymorphisms on lung cancer risk (Persson et al, 1999;Lin et al, 2000;London et al, 2000;To-Figueras et al, 2001;Wu et al, 2001;Zhao et al, 2002;Zhou et al, 2001Zhou et al, , 2002, resulting in somewhat inconsistent findings. Recently, Lee et al (2002) performed a meta-analysis of seven published studies and a pooled analysis of four published and four unpublished studies to investigate the association of the mEH polymorphisms and lung cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk

et al. 2003

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Microsomal epoxide hydrolase (mEH) plays a dual role in the detoxification and activation of tobacco procarcinogens. Two polymorphisms affecting enzyme activity have been described in the exons 3 and 4 of the mEH gene, which result in the substitution of amino acids histidine to tyrosine at residue 113, and arginine to histidine at residue 139, respectively. We performed a hospitalbased case -control study consisting of 277 newly diagnosed lung cancer patients and 496 control subjects to investigate a possible association between these two polymorphisms and lung cancer risk. The polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism and TaqMan assay using DNA from peripheral white blood cells. Logistic regression was performed to calculate odds ratios (ORs), confidence limits (CL) and to control for possible confounders. The exon 3 polymorphism of the mEH gene was associated with a significantly decreased risk of lung cancer. The adjusted OR, calculated relative to subjects with the Tyr113/Tyr113 wild type, for the His113/His113 genotype was 0.38 (95% CL 0.20 -0.75). An analysis according to histological subtypes revealed a statistically significant association for adenocarcinomas; the adjusted OR for the His113/His113 genotype was 0.40 (95% CL 0.17 -0.94). In contrast, no relationship between the exon 4 polymorphism and lung cancer risk was found. The adjusted OR, calculated relative to the His139/His139 wild type, was for the Arg139/Arg139 genotype 1.83 (0.76 -4.44). Our results support the hypothesis that genetically reduced mEH activity may be protective against lung cancer.

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Section: Discussionmentioning

confidence: 99%

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk

et al. 2003

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“…In experimental systems, it has been shown that GSTP1 plays a critical role in the development of lung carcinogenesis following exposure to tobaccorelated carcinogens, such as the detoxification of electrophilic diol-epoxides produced by the metabolism of polycyclic aromatic hydrocarbons [5,6] and aberrant promoter methylation of the P16 tumor suppressor gene and the O(6)-methylguanine-DNA methyltransferase (MGMT) DNA repair gene [13,14] . However, some epidemiological studies demonstrating the association between polymorphisms of GSTP1 and lung cancer risk yielded inconclusive results [15][16][17][18][19][20][21] . Thus, further study of GSTP1 as a candidate gene in lung cancer risk alone or at the genome-wide level was necessary.…”

Section: Introductionmentioning

confidence: 99%

HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population

Feng

Mei

et al. 2014

Acta Pharmacol Sin

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Aim: Myeloperoxidase (MPO) and glutathione S-transferase pi 1 (GSTP1) are important carcinogen-metabolizing enzymes. The aim of this study was to investigate the association between the common polymorphisms of MPO and GSTP1 genes and lung cancer risk in Chinese Han population. Methods: A total of 266 subjects with lung cancer and 307 controls without personal history of the disease were recruited in this case control study. The tagSNPs approach was used to assess the common polymorphisms of MOP and GSTP1 genes and lung cancer risk according to the disequilibrium information from the HapMap project. The tagSNP rs7208693 was selected as the polymorphism site for MPO, while the haplotype-tagging SNPs rs1695, rs4891, rs762803 and rs749174 were selected as the polymorphism sites for GSTP1. The gene polymorphisms were confirmed using real-time PCR, cloning and sequencing. Results: The four GSTP1 haplotype-tagging SNPs rs1695, rs4891, rs762803 and rs749174, but not the MPO tagSNP rs7208693, exhibited an association with lung cancer susceptibility in smokers in the overall population and in the studied subgroups. When Phase 2 software was used to reconstruct the haplotype for GSTP1, the haplotype CACA (rs749174+rs1695 + rs762803+rs4891) exhibited an increased risk of lung cancer among smokers (adjust odds ratio 1.53; 95%CI 1. 04-2.25, P=0.033). Furthermore, diplotype analyses demonstrated that the significant association between the risk haplotype and lung cancer. The risk haplotypes co-segregated with one or more biologically functional polymorphisms and corresponded to a recessive inheritance model. Conclusion: The common polymorphisms of the GSTP1 gene may be the candidates for SNP markers for lung cancer susceptibility in Chinese Han population.

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“…In contrast to highly reactive epoxides, dihydrodiols are mostly inert and can be excreted after conjugating to glutathione (4). However, EH may not always be protective.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non-small cell lung cancer

Lin

Huang²,

Fan³

et al. 2007

Oncol Rep

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Abstract. Genetic polymorphisms of microsomal epoxide hydrolase (mEH) have been associated with increased risk of lung cancer. However, expression of mEH and its clinical significance in non-small cell lung cancer (NSCLC) have not been investigated. In this study we investigated the expression and genetic polymorphism of mEH in non-small cell lung cancer (NSCLC) patients. Genetic polymorphism was determined by restriction fragment length polymorphism of polymerase chain reaction (PCR) products. CGT/ 418 CGT in exon 4. Of the 72 NSCLC biopsies analyzed, mEH was expressed in 60 (83%) surgical specimens, and the major allelic expression pattern was fast type (Tyr113) in exon 3 (90.3%) and slow type (His139) in exon 4 (100%). Immunohistochemical staining showed that mEH was expressed in 326 of 423 (77.0%) tumor (lung tissue) specimens and in 48 of 93 (51.6%) metastatic lymph nodes. A significant difference in patient survival was found when mEH expression and adriamycin-containing chemotherapy were used to group patients (p=0.0167). In conclusion, with the combination of fast type (Tyr113) and slow type (His139), the mEH enzyme expressed in most NSCLC patients may have intermediate activity. Our findings indicate that with respect to cancer risk and disease progression, the expression level of mEH is as important as genetic polymorphism. In addition, mEH expression in NSCLC could be involved in drug resistance and prognosis of patients.

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Lung cancer susceptibility in relation to combined polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase P1

Cited by 49 publications

References 19 publications

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk

HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population

Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non-small cell lung cancer

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