Sahin Onder, Arikan Soykan, Oltulu Yasemin Musteri, Coskunpinar Ender, Eren Ayşe, Cacina Canan, Guler Erkan, Yaylim Ilhan
Neuromuscular Pathology Unit, Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Genet Test Mol Biomarkers. 2012 May;16(5):423-8. doi: 10.1089/gtmb.2011.0223. Epub 2012 Feb 21.
Metabolism of chemical carcinogens, including their activation and detoxification, plays a key role in carcinogenesis. Microsomal epoxide hydrolase (EPHX1) has an important role in the metabolism of polycyclic aromatic hydrocarbons and detoxification of procarcinogens. The aim of this study was to investigate the association between colorectal cancer (CRC) development and EPHX1 gene polymorphisms. We investigated the polymorphisms in exon 3 (T>C, Tyr113His) and exon 4 (A>G, His139Arg) of the EPHX1 gene in 68 CRC patients and 116 controls by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the Try113Try, Try113His, and His113His for EPHX1 exon 3 were 37.9%, 55.2%, and 6.9% in controls and 39.7%, 42.6%, and 17.6% in CRC patients, respectively. Frequencies of EPHX1 exon 4 genotypes were 62.1% His139His, 37.9% His139Arg, and 0% Arg139Arg in the control group and 76.5% His139His, 22.1% His139Arg, and 1.5% Arg139Arg in the patient group. Individuals carrying the EPHX1 exon 3 His113His genotype had a 2.5-fold increased risk (p=0.024), and those carrying the EPHX1 exon 4 His139Arg genotype had decreased risk of CRC compared with controls (p=0.019). Even though exon 3 Tyr113His and exon 4 His139Arg polymorphisms for EPHX1 gene appear to be important factors for CRC risk, further investigations with larger study groups are needed to fully elucidate the role of these polymorphisms in the development of CRC.
化学致癌物的代谢，包括其活化和解毒，在致癌过程中起着关键作用。微粒体环氧化物水解酶（EPHX1）在多环芳烃的代谢和前致癌物的解毒中具有重要作用。本研究的目的是探讨结直肠癌（CRC）发生与EPHX1基因多态性之间的关联。我们通过聚合酶链反应-限制性片段长度多态性方法，对68例CRC患者和116例对照者的EPHX1基因外显子3（T>C，Tyr113His）和外显子4（A>G，His139Arg）中的多态性进行了研究。EPHX1外显子3的Try113Try、Try113His和His113His频率在对照组中分别为37.9%、55.2%和6.9%，在CRC患者中分别为39.7%、42.6%和17.6%。EPHX1外显子4基因型频率在对照组中为62.1%His139His、37.9%His139Arg和0%Arg139Arg，在患者组中为76.5%His139His、22.1%His139Arg和1.5%Arg139Arg。与对照组相比，携带EPHX1外显子3 His113His基因型的个体患CRC的风险增加了2.5倍（p=0.024），而携带EPHX1外显子4 His139Arg基因型的个体患CRC的风险降低（p=0.019）。尽管EPHX1基因的外显子3 Tyr113His和外显子4 His139Arg多态性似乎是CRC风险的重要因素，但需要更大规模的研究组进行进一步调查，以充分阐明这些多态性在CRC发生中的作用。
