van der Logt E M J, Bergevoet S M, Roelofs H M J, van Hooijdonk Z, te Morsche R H M, Wobbes T, de Kok J B, Nagengast F M, Peters W H M
Department of Gastroenterology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
Carcinogenesis. 2004 Dec;25(12):2407-15. doi: 10.1093/carcin/bgh251. Epub 2004 Aug 19.
Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. To determine whether genetic polymorphisms in detoxification enzymes predispose to the development of CRC, 371 patients with sporadic CRC and 415 healthy controls were genotyped for polymorphisms in the important detoxification enzymes UDP-glucuronosyltransferase UGT1A1, UGT1A6, UGT1A7 and UGT1A8, and glutathione S-transferase GSTA1, GSTM1, GSTP1 and GSTT1. Patients and controls were all of Caucasian origin. DNA was isolated from either blood or tissue and tested by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Logistic regression analyses showed significant age- and gender-adjusted risks for CRC associated with variant genotypes of UGT1A6 [OR 1.5, 95% (confidence interval) CI 1.03-2.3] and UGT1A7 (OR 2.4, 95% CI 1.3-4.6), whereas no associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, the data suggest that the presence of variant UGT1A6 and UGT1A7 genotypes with expected reduced enzyme activities, might enhance susceptibility to CRC.
结直肠癌（CRC）是西方世界最常见的恶性肿瘤之一，其发病率呈上升趋势，并且与遗传和生活方式因素有关。个体对CRC的易感性可能部分归因于胃肠道解毒能力的差异。解毒酶的基因多态性可能导致解毒活性的变化，进而可能影响有毒/致癌化合物的水平，这可能会影响患CRC的风险。为了确定解毒酶的基因多态性是否易患CRC，对371例散发性CRC患者和415例健康对照进行了重要解毒酶尿苷二磷酸葡萄糖醛酸基转移酶UGT1A1、UGT1A6、UGT1A7和UGT1A8以及谷胱甘肽S-转移酶GSTA1、GSTM1、GSTP1和GSTT1多态性的基因分型。患者和对照均为白种人。从血液或组织中分离DNA，并通过聚合酶链反应随后进行限制性片段长度多态性分析进行检测。逻辑回归分析显示，与UGT1A6的变异基因型[比值比（OR）1.5，95%（置信区间）CI 1.03 - 2.3]和UGT1A7（OR 2.4，95%CI 1.3 - 4.6）相关的CRC在年龄和性别调整后的风险显著，而未发现CRC与上述其他多态性基因之间存在关联。总之，数据表明具有预期降低酶活性的变异UGT1A6和UGT1A7基因型的存在可能会增加对CRC的易感性。
