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UGT1A8基因多态与结直肠癌的相关性
引用本文:王敏,孙德峰,李延青,陈建,郭辰虹,刘福国,袁孟彪. UGT1A8基因多态与结直肠癌的相关性[J]. 世界华人消化杂志, 2005, 13(15): 1819-1823
作者姓名:王敏  孙德峰  李延青  陈建  郭辰虹  刘福国  袁孟彪
作者单位:1. 山东大学齐鲁医院干部保健科,山东省,济南市,250012
2. 山东省烟台护士学校遗传教研室,山东省,烟台市,264000
3. 山东大学齐鲁医院消化内科,山东省,济南市,250012
4. 山东大学医学遗传学研究所,山东省,济南市,250012
基金项目:国家自然科学基金资助项目,No.30370634~~
摘    要:

关 键 词:结直肠癌  葡萄糖醛酸转移酶1A8  多态性  易感性
修稿时间:2005-05-31

Polymorphism of UDP-glucuronosyltransferase UGT1A8 gene in human colorectal cancer
Min Wang,De-Feng Sun,Yan-Qing Li,Jian Chen,Chen- Hong Guo,Fu-Guo Liu,Meng-Biao Yuan. Polymorphism of UDP-glucuronosyltransferase UGT1A8 gene in human colorectal cancer[J]. World Chinese Journal of Digestology, 2005, 13(15): 1819-1823
Authors:Min Wang  De-Feng Sun  Yan-Qing Li  Jian Chen  Chen- Hong Guo  Fu-Guo Liu  Meng-Biao Yuan
Affiliation:Min Wang,Department of Health Care,Qilu Hospital of Shandong University,Jinan 250012,Shandong Province,China De-Feng Sun,Yantai Nursing School,Yantai 264000,Shandong Province,China Yan-Qing Li,Jian Chen,Fu-Guo Liu,Meng-Biao Yuan,Department of Gastroenterology,Qilu Hospital of Shandong University,Jinan 250012,Shandong Province,China Chen-Hong Guo,Institute of Medical Genetics,Shandong University,Jinan 250012,Shandong Province,China
Abstract:AIM: To explore the relationship between the polymorphism of UDP-glucuronosyltransferase UGT1A8 gene and human colorectal cancer (CRC). METHODS: One hundred and nine cases of colorectal cancer and normal controls (NC), respectively, were collected for analysis. Genomic DNA was prepared from full blood samples. The amplification of UGT1A8 exon-1 sequences was performed using exon-1 specific primer. And the products were visualized by gel electrophoresis and the fragments were purified. The extracted DNA was subcloned into TOPO TA plasmid and the insert was se-quenced for the allelic specificity. Two-tailed Fisher's exact test was used to determine the differences of allelic genotypes between CRC and NC group. Odds ratios (ORs) and confidence interval (CI) were calculated to evaluate the relationship between the gene polymorphism and the grades of CRC. The predisposition factors of CRC were analyzed by Logistics. RESULTS: Three mutations were identified in UGT1A8 exon-1. The allele frequency of wild UGT1A8*1 was higher in controls when compared with that in CRC (P = 0.047, OR=0.51,95% CI: 0.28-0.79), suggesting that this allele was a protective factor. The frequency of mutant UGT1 A8*3 was significantly lower in controls than that in CRC (P= 0.003, OR = 9.63, 95% Cl: 2.12-7.79), indicating UGT1 A8*3 as a risk factor of CRC. The expression of homozygous UGT1 A8*1 was markedly higher in controls than that in CRC (P = 0.045). Both heterozygous UGT1 A8*1/*3 and UGT1 A8*2/*3 were more significantly expressed in CRC as compared with that in controls (P<0.05, OR = 5.03, 95% Cl: 2.25-5.99; P = 0.003, OR =12.90, 95% Cl: 2.68-6.15). Logistic regression analysis demonstrated that the occurrence of CRC was mainly related to the presence of polymorphic UGT1A8 alleles (P= 0.029), but not the sex of the patients (P = 0.25). CONCLUSION: The high incidence of UGT1A8 polymorphism exists in the patients with colorectal cancer. UGT1 A8*1 allele is a protective factor and UGT1 A8*3 allele is a risk factor for CRC. Homozygous UGT1 A8*1/*3 and UGT1 A8*2/*3 are also associated with the high occurrence of CRC.
Keywords:Colorectal cancer  UDP-glucuronosy-ltransferase UGTl A8  Polymorphism  Predisposition
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