Bajro Marija Hiljadnikova, Josifovski Toni, Panovski Milco, Jankulovski Nikola, Nestorovska Aleksandra Kapedanovska, Matevska Nadica, Petrusevska Natalija, Dimovski Aleksandar J
Faculty of Pharmacy, Saints Cyril and Methodius University, Skopje, Republic of Macedonia.
Cancer Genet. 2012 Apr;205(4):163-7. doi: 10.1016/j.cancergen.2012.01.015.
Uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) is the key hepatic detoxification enzyme involved in the biotransformation of many carcinogens implicated in the development of colon, breast, and prostate cancers in humans. A polymorphism in the UGT1A1 promoter containing a TA-repeat element [(TA)5-8TAA] is involved in the modulation of UGT1A1 transcriptional activity. The wild-type activity is associated with the (TA)6TAA allele (UGT1A11), whereas UGT1A1 expression decreases with the increase of the TA-repeat number. We hypothesize that the low-activity allele UGT1A128 with seven TA repeats is associated with a higher risk for colorectal cancer. Our study involved 168 patients with histopathologically confirmed sporadic colorectal cancer and a control group of 96 individuals with no personal history of colorectal cancer. We detected a higher frequency of UGT1A128 than the wild-type UGT1A11 allele in colorectal cancer patients as compared with that of controls (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.07-2.26, P = 0.021). The frequency of genotypes containing the UGT1A128 allele in the homozygous or heterozygous state was significantly higher than the frequency of the wild-type UGT1A11/1 genotype in colorectal cancer patients as compared with controls (OR = 2.0, 95% CI = 1.19-3.34, P = 0.007). Our results indicate that the UGT1A128 allele is a risk factor for colorectal cancer in the Macedonian male population, whereas no significant risk was detected among women.
尿苷二磷酸葡萄糖醛酸葡萄糖醛酸基转移酶1A1（UGT1A1）是肝脏中关键的解毒酶，参与多种与人类结肠癌、乳腺癌和前列腺癌发生相关的致癌物的生物转化。UGT1A1启动子中的一个多态性包含TA重复元件[（TA）5 - 8TAA]，它参与UGT1A1转录活性的调节。野生型活性与（TA）6TAA等位基因（UGT1A11）相关，而UGT1A1的表达随着TA重复数目的增加而降低。我们推测具有七个TA重复的低活性等位基因UGT1A128与结直肠癌的较高风险相关。我们的研究纳入了168例经组织病理学确诊的散发性结直肠癌患者以及96例无结直肠癌个人史的个体作为对照组。与对照组相比，我们在结直肠癌患者中检测到UGT1A128的频率高于野生型UGT1A11等位基因（优势比[OR]=1.55，95%置信区间[CI]=1.07 - 2.26，P = 0.021）。与对照组相比，结直肠癌患者中纯合或杂合状态包含UGT1A128等位基因的基因型频率显著高于野生型UGT1A11/1基因型频率（OR = 2.0，95% CI = 1.19 - 3.34，P = 0.007）。我们的结果表明，UGT1A128等位基因是马其顿男性人群结直肠癌的一个危险因素，而在女性中未检测到显著风险。
