Microsomal epoxide hydrolase (EPHX1) is an evolutionarily highly conserved biotransformation enzyme for converting epoxides to diols. Notably, the enzyme is able to either detoxify or bioactivate a wide range of substrates. Mutations and polymorphic variants in the EPHX1 gene have been associated with susceptibility to several human diseases including cancer. This review summarizes the key knowledge concerning EPHX1 gene and protein structure, expression pattern and regulation, and substrate specificity. The relevance of EPHX1 for human pathology is especially discussed.

• Klíčová slova
• Disease, EPHX1, Function, Gene, Genotype, Structure,
• MeSH
• alkoholické nemoci jater genetika   metabolismus   MeSH
• epoxid hydrolasy genetika   metabolismus   MeSH
• genetická predispozice k nemoci genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• mutace * MeSH
• nádory genetika   metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• rizikové faktory MeSH
• substrátová specifita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• EPHX1 protein, human MeSH Prohlížeč
• epoxid hydrolasy MeSH

PURPOSE: Colorectal cancer is an important cause of mortality in the developed world. Hereditary forms are due to germ-line mutations in APC, MUTYH, and the mismatch repair genes, but many cases present familial aggregation but an unknown inherited cause. The hypothesis of rare high-penetrance mutations in new genes is a likely explanation for the underlying predisposition in some of these familial cases. METHODS: Exome sequencing was performed in 43 patients with colorectal cancer from 29 families with strong disease aggregation without mutations in known hereditary colorectal cancer genes. Data analysis selected only very rare variants (0-0.1%), producing a putative loss of function and located in genes with a role compatible with cancer. Variants in genes previously involved in hereditary colorectal cancer or nearby previous colorectal cancer genome-wide association study hits were also chosen. RESULTS: Twenty-eight final candidate variants were selected and validated by Sanger sequencing. Correct family segregation and somatic studies were used to categorize the most interesting variants in CDKN1B, XRCC4, EPHX1, NFKBIZ, SMARCA4, and BARD1. CONCLUSION: We identified new potential colorectal cancer predisposition variants in genes that have a role in cancer predisposition and are involved in DNA repair and the cell cycle, which supports their putative involvement in germ-line predisposition to this neoplasm.

• MeSH
• dědičné nepolypózní kolorektální nádory genetika   MeSH
• exom * MeSH
• genetická predispozice k nemoci * MeSH
• genetická variace * MeSH
• genetické poradenství MeSH
• kolorektální nádory genetika   MeSH
• lidé MeSH
• reprodukovatelnost výsledků MeSH
• rodokmen MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• zárodečné mutace MeSH
• ztráta heterozygozity MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH