Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/40466
標題: Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non-small cell lung cancer
作者: Lin, T.S.
邱繡河
Huang, H.H.
Fan, Y.H.
Chiou, S.H.
Chow, K.C.
周寬基
關鍵字: microsomal epoxide hydrolase
non-small cell lung cancer
genetic
polymorphism
allelic expression pattern
cigarette smoking
drug
resistance
breast-cancer
risk
susceptibility
carcinoma
genotypes
variants
exposure
smoking
enzymes
tissues
期刊/報告no:: Oncology Reports, Volume 17, Issue 3, Page(s) 565-572.
摘要: 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. The allelic expression pattern as well as expression level of mEH were determined by reverse transcription-PCR (RT-PCR), cDNA sequencing, sequence alignment, immunoblotting and immunohistochemistry. Genotype distributions of mEH in Taiwan's NSCLC patients were 44.4% of (340)TAC/(340)TAC, 48.6% of (340)TAC/(340)CAC, and 7.0% of (340)CAC/(340)CAC in exon 3, and 80.6% of (418)CAT/(418)CAT, 19.4% of (418)CAT/(418)CGT and 0% of (418)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 (His 139), 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.
URI: http://hdl.handle.net/11455/40466
ISSN: 1021-335X
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