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黎巴嫩人群中CYP1A1、CYP2E1和GSTM1基因多态性与结直肠癌和胃癌易感性

CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and susceptibility to colorectal and gastric cancer among Lebanese.

作者信息

Darazy Mohamad, Balbaa Mahmoud, Mugharbil Anas, Saeed Hesham, Sidani Hassan, Abdel-Razzak Ziad

机构信息

Department of Biological Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon.

出版信息

Genet Test Mol Biomarkers. 2011 Jun;15(6):423-9. doi: 10.1089/gtmb.2010.0206. Epub 2011 Mar 8.

Abstract

Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM10/0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A12A and CYP2E16 alone are not significantly associated with GI cancer development, although CYP1A12A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A12A/2A combined with GSTM10/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.

摘要

编码参与化学致癌物代谢的酶的基因突变可显著影响细胞转化和癌症发生的风险。黎巴嫩常住人口在过去几年中癌症发病率急剧上升。代谢酶基因多态性与胃肠道(GI)癌症发病率之间的关系此前未被研究。本研究的目的是调查黎巴嫩人群中CYP1A1、CYP2E1和GSTM1基因多态性与GI癌症发病率之间的关系。从患者和健康对照中收集血液和/或石蜡包埋的活检样本。通过聚合酶链反应和聚合酶链反应-限制性片段长度多态性确定基因型。本病例对照研究的结果表明,在所考虑的多态性方面,所研究的黎巴嫩人群总体上与白种人群相似。此外,GSTM10/0基因型是胃癌(优势比=4.1;95%置信区间:1.2-14.5)和结直肠癌(优势比=3.8;95%置信区间:1.7-8.5)的显著风险因素;另一方面,单独的CYP1A12A和CYP2E16与GI癌症发生无显著关联,尽管CYP1A12A在患者中更常见。在CYP1A12A/2A与GSTM10/*0组合的患者中,观察到胃癌风险显著增加且具有统计学意义,增加了36.5倍。对黎巴嫩人群的遗传风险因素和易感基因多态性进行调查有助于更好地理解GI癌症的病因。

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