van der Logt E M J, te Morsche R H M, Groenendaal N, Roelofs H M J, de Metz M, van der Stappen J W, Nagengast F M, Peters W H M
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
Oncol Res. 2009;17(7):323-9. doi: 10.3727/096504009787721203.
Colorectal cancer (CRC) is one of the most common malignancies in the Western world. CRC is strongly associated with lifestyle factors. Susceptibility to CRC may be partly due to deficient detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes result in variations in detoxification activities, which might influence the levels of carcinogens in the gastrointestinal tract, influencing the risk for CRC. To determine whether a genetic polymorphism in the detoxification enzyme UDP-glucuronosyltransferase 2B7 (UGT2B7) predisposes to CRC, 411 Caucasian patients with sporadic CRC and 600 Caucasian controls recruited from the same geographic area were genotyped for the functional UGT2B7 H268Y polymorphism. DNA was isolated and tested by a dual-color real-time polymerase chain reaction assay. Overall, no differences in genotype distributions between patients with CRC and controls were observed. When analyzed with respect to tumor location, a shift from the UGT2B7I 2 into the UGT2B722 genotype was seen in patients with proximal CRC (OR 1.80, 95% CI 1.11-2.89). In the male patient subpopulation an even stronger association was observed (11 + 12 vs. 22: OR 2.17, 95% CI 1.11-4.04; 12 vs. 22: OR 2.19, 95% CI 1.10-4.37). No associations with respect to tumor stage were seen. In conclusion, the frequency of the UGT2B722 genotype is higher in CRC patients with proximal location of the tumor, especially in males, which suggests that this genotype is associated with an increased risk for proximal CRC.
结直肠癌（CRC）是西方世界最常见的恶性肿瘤之一。CRC与生活方式因素密切相关。对CRC的易感性可能部分归因于胃肠道解毒能力不足。解毒酶的基因多态性导致解毒活性的差异，这可能会影响胃肠道中致癌物的水平，进而影响患CRC的风险。为了确定解毒酶尿苷二磷酸葡萄糖醛酸基转移酶2B7（UGT2B7）的基因多态性是否易患CRC，对411名来自同一地理区域的散发性CRC白种人患者和600名白种人对照进行了功能性UGT2B7 H268Y多态性基因分型。通过双色实时聚合酶链反应分析分离并检测DNA。总体而言，未观察到CRC患者与对照之间基因型分布的差异。当按肿瘤位置分析时，近端CRC患者中出现了从UGT2B712基因型向UGT2B722基因型的转变（比值比1.80，95%可信区间1.11 - 2.89）。在男性患者亚组中观察到更强的关联（11 + 12与22相比：比值比2.17，95%可信区间1.11 - 4.04；12与22相比：比值比2.19，95%可信区间1.10 - 4.37）。未观察到与肿瘤分期相关的关联。总之，肿瘤位于近端的CRC患者中UGT2B722基因型的频率较高，尤其是男性，这表明该基因型与近端CRC风险增加有关。
