title: Polymorphic expression of UDP-glucuronosyltransferase UGTlA gene in human colorectal cancer.
abstract: BACKGROUND
  Polymorphism of genes encoding drug-metabolizing enzymes is known to play an important role in increased susceptibility of colorectal cancer. UGT1A gene locus has been suggested to define tissue-specific glucuronidation activity. Reduced capacity of glucuronidation is correlated with the development of colorectal cancer. Therefore, we sought to explore polymorphism of UGTlA gene in human colorectal cancer.
  
  
  METHODS
  Cancerous and healthy tissues were obtained from selectedpatients. Blood samples were collected and UGTlA mRNA transcriptions were analyzed. Genomic DNA was prepared and UGTlA8 exon-1 sequences were amplified, visualized and purified. The extracted DNA was subcloned and sequenced. Two-tailed Fisher's exact test, Odds ratios (ORs), confidence interval (CIs) and Logistics Regression Analysis were used for statistical analysis.
  
  
  RESULTS
  UGTlA mRNA expression was reduced in cancerous tissues compared with healthy tissues from the same patient . The UGTlA mRNA expression of healthy tissue in study patients was lower than control . The mRNA expression of cancerous tissue was down-regulated in UGTlAl, 1A3, 1A4, lA6, 1A9 and up-regulated in UGTlA8 and UGTlAl0 UGT1A5 and UGT1A7 were not expressed in colonic tissue of either group. The allele frequency of WT UGTlA8*1 was higher (p = 0.000), frequency of UGTlA8*3 was lowered in control group (p = 0.000). The expression of homozygous UGTlA8*1 was higher in control group (p = 0.000). Higher frequency of both heterozygous UGTlA8*1/*3 and UGTlA8*2/*3 were found in study group (p = 0.000; p = 0.000). The occurrence of colorectal cancer was mainly related to the presence of polymorphic UGTlA8*3 alleles (p = 0.000).
  
  
  CONCLUSIONS
  Regulation of human UGT1A genes is tissue-specific. Individual variation in polymorphic expressions of UGTlA gene locus was noted in all types of colonic tissue tested, whereas hepatic tissue expression was uniform. The high incidence of UGTlA8 polymorphism exists in colorectal cancer patients. UGTlA8*1 allele is a protective factor and UGTlA8*3 allele is a risk factor.
authors.affiliation: Department of Geriatrics and Gastroenterology, Qi-Lu Hospital of Shandong University, Key Laboratory of Proteomics of Shandong Province, Jinan, Shandong Province, China. doctorminmin@163.com
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: De-Feng
authors.initials: DF
authors.lastname: Sun
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Qing
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Ji-Zhuang
authors.initials: JZ
authors.lastname: Luo
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000368:Aged; D000483:Alleles; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D059368:RNA Isoforms; D012333:RNA, Messenger / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D059368:RNA Isoforms; D012333:RNA, Messenger; D000099148:UGT1A1 Enzyme