Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population

Hong Tao, Kazuya Shinmura, Masaya Suzuki, Suminori Kono, Ryuichi Mibu, Masao Tanaka, Yoshihiro Kakeji, Yoshihiko Maehara, Takeshi Okamura, Kouji Ikejiri, Kitaroh Futami, Youichi Yasunami, Takafumi Maekawa, Kenji Takenaka, Hitoshi Ichimiya, Nobutoshi Imaizumi, Haruhiko Sugimura

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)355-360
Number of pages6
JournalCancer Science
Volume99
Issue number2
DOIs
Publication statusPublished - Feb 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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