Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population
Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population
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DOI：
10.1111/j.1349-7006.2007.00694.x
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发表时间：
2008-02-01
期刊：
影响因子：
5.7
通讯作者：
Sugimura, Haruhiko
中科院分区：
文献类型：
--
作者：
Tao, Hong;Shinmura, Kazuya;Sugimura, Haruhiko
MUTYH 基因编码 DNA 糖基化酶，该酶可以启动碱基切除修复途径，并通过切除与 8-羟基鸟嘌呤错配的腺嘌呤来防止 G:C > T:A 颠换。 MUTYH 的双等位基因种系突变已被证明可以预测家族性和散发性多发性结直肠腺瘤和癌，然而，MUTYH 的单核苷酸多态性 (SNP) 与散发性结直肠癌 (CRC) 风险之间是否存在关联仍不清楚。在这项研究中，我们在日本九州的 685 名 CRC 患者和 778 名对照受试者中调查了 4 个 MUTYH SNP（IVS1+11C > T、IVS6+35G > A、IVS10-2A > G 和 972G > C (Gln324His)）与 CRC 风险增加的关联。 IVS1+11T 与 CRC 风险增加（比值比 [OR]：1.43；95% 置信区间 [CI]：1.012-2.030；P = 0.042）和基于四个 SNP 的五种单倍型之一（IVS1+11T - IVS6+35G - IVS10-2A - 972C）之间存在统计学上显着的关联。含有 IVS1+11T 的 (TGAC) 单倍型被证明与 CRC 风险增加相关（OR，1.43；95% CI，1.005-2.029；P = 0.046）。亚位点特异性分析表明，TGAC 单倍型与远端结肠癌风险增加具有统计学显着相关性（P = 0.013），但与近端结肠癌或直肠癌风险增加无关。此外，发现 IVS1+11C > T 与 -280G > A 和 1389G > C (Thr463Thr) 完全连锁不平衡。结果表明，具有-280A/IVS1+11T/1389C基因型或TGAC单倍型的日本人易患CRC。
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.