title: Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population.
abstract: The MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8-hydroxyguanine. Biallelic germline mutations of MUTYH have been shown to predict familial and sporadic multiple colorectal adenomas and carcinomas, however, whether there is an association between single nucleotide polymorphisms (SNPs) of MUTYH and sporadic colorectal cancer (CRC) risk has remained unclear. In this study we investigated four MUTYH SNPs, IVS1+11C > T, IVS6+35G > A, IVS10-2A > G, and 972G > C (Gln324His), for an association with increased CRC risk in a population-based series of 685 CRC patients and 778 control subjects from Kyushu, Japan. A statistically significant association was demonstrated between IVS1+11T and increased CRC risk (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.012-2.030; P = 0.042) and one of the five haplotypes based on the four SNPs, the IVS1+11T - IVS6+35G - IVS10-2A - 972C (TGAC) haplotype containing IVS1+11T, was demonstrated to be associated with increased CRC risk (OR, 1.43; 95% CI, 1.005-2.029; P = 0.046). Subsite-specific analysis showed that the TGAC haplotype was statistically significantly (P = 0.013) associated with an increased risk of distal colon, but not proximal colon or rectal cancer. Furthermore, IVS1+11C > T was found to be in complete linkage disequilibrium with -280G > A and 1389G > C (Thr463Thr). The results indicated that Japanese individuals with - 280A/IVS1+11T/1389C genotypes or the TGAC haplotype are susceptible to CRC.
authors.affiliation: First Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Masaya
authors.initials: M
authors.lastname: Suzuki
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mibu
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamura
authors.forename: Kouji
authors.initials: K
authors.lastname: Ikejiri
authors.forename: Kitaroh
authors.initials: K
authors.lastname: Futami
authors.forename: Youichi
authors.initials: Y
authors.lastname: Yasunami
authors.forename: Takafumi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takenaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichimiya
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Imaizumi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase