title: Association between polymorphisms in the XRCC1 and GST genes, and CpG island methylation status in colonic mucosa in ulcerative colitis.
abstract: CpG island hypermethylation (CIHM) is frequently observed in the colonic mucosa in ulcerative colitis (UC) and is deeply involved in UC-associated colorectal carcinogenesis. We evaluated the influence of common polymorphisms related to DNA repair or xenobiotic pathway (XRCC1, GSTP1, GSTT1, and GSTM1) on the individual susceptibility to CIHM status in the non-neoplastic rectal mucosa in UC patients. XRCC1 Arg399Gln and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 84 UC patients without neoplastic lesions, in relation to CIHM in the rectal mucosa of three candidate CpG loci (p14, p16, and CDH1) assessed by methylation-specific polymerase chain reaction. XRCC1 codon 399 Arg/Gln genotype (odds ratio (OR) = 0.31, 95%CI = 0.12-0.81, p = 0.017) and 399 Gln carrier (GlnGln+Arg/Gln: OR = 0.30, 95%CI = 0.12-0.76, p = 0.01) were significantly associated with reduced susceptibility to CIHM of the CDH1 promoter. GSTP1 Val carrier (Ile Val+Val/Val) also held a significantly lower susceptibility to CIHM of the p16 promoter (OR = 0.26, 95%CI = 0.08-0.86, p = 0.028). In contrast, GSTT1 present genotype (OR = 3.16, 95%CI = 1.27-7.89, p = 0.01) was significantly associated with increased susceptibility to CIHM of the same gene. XRCC1 codon 399 Gln/Gln genotype was significantly associated with lower mean number of CIHM when compared to the Arg/Arg genotype (1.53 ± 1.01 vs. 0.63 ± 1.06, p = 0.024). In addition, the GSTP1 Ile/Val carrier (Ile/Val+Val/Val) was also significantly associated with lower mean number of CIHM (1.43 ± 1.03 vs. 0.84 ± 1.07, p = 0.03). XRCC1 Arg399Gln and GSTP1 Ile104Val polymorphisms may influence the CIHM status in the rectal mucosa of UC patients and may be substantially involved in UC-associated carcinogenesis.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. tomomiccyu@yahoo.co.jp
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Joh
authors.initials: J
authors.lastname: Yonemura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
mesh_terms: D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C413545:glutathione S-transferase T1