Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population.
Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population.
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DOI：
10.1093/carcin/bgh335
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发表时间：
2004-09
期刊：
影响因子：
4.7
通讯作者：
H. Yamamoto;H. Hanafusa;M. Ouchida;M. Yano;Hiromitsu Suzuki;M. Murakami;M. Aoe;N. Shimizu;K. Nakachi;K. Shimizu
中科院分区：
文献类型：
--
作者：
H. Yamamoto;H. Hanafusa;M. Ouchida;M. Yano;Hiromitsu Suzuki;M. Murakami;M. Aoe;N. Shimizu;K. Nakachi;K. Shimizu
EXO1是RAD2核酸酶家族的一员，在DNA复制、修复和重组中起作用。我们研究了EXO1基因外显子10 （T439M）和外显子13 （P757L）的单核苷酸多态性（snp）与结直肠癌发生、进展和转移的关系。对于T439M，在调整年龄、性别和吸烟状况后，Thr/Met基因型[比值比(OR) = 2.03, 95%可信区间（CI） 1.04-3.98]和Thr/Met和Met/Met基因型联合（OR = 2.37, 95% CI 1.23-4.56）与结直肠癌的发生有显著相关性。对于P757L，将Pro/Leu和Pro/Pro基因型合并作为对照时，Leu/Leu基因型患者结直肠癌风险降低（校正OR = 0.398, 95% CI 0.183-0.866）。当以Pro/Leu基因型为参照时，Leu/Leu基因型的风险也降低（调整OR = 0.373, 95% CI 0.164-0.850）。携带两种推定风险基因型（T439M为Thr/Met和Met/Met， P757L为Pro/Leu）的个体与携带两种低风险基因型的个体相比，调整后OR为4.95 （95% CI 1.56-15.7）。微卫星不稳定性（microsatellite instability， MSI）分析显示，携带两种假定风险基因型的个体的肿瘤MSI阳性的频率往往高于携带两种低风险基因型的患者，尽管EXO1基因型和MSI状态之间没有发现显著的相关性。这是第一份为EXO1基因多态性与结直肠癌风险相关提供证据的报告。结直肠癌患者的EXO1基因型与任何临床病理特征无关。
EXO1 is a member of the RAD2 nuclease family and functions in DNA replication, repair and recombination. We investigated the relationship of single nucleotide polymorphisms (SNPs) at exon 10 (T439M) and exon 13 (P757L) of the EXO1 gene with development, progression and metastasis of colorectal cancer. For T439M, the Thr/Met genotype [odds ratio (OR) = 2.03, 95% confidence interval (CI) 1.04-3.98] and Thr/Met and Met/Met genotypes combined (OR = 2.37, 95% CI 1.23-4.56) demonstrated significant association with the development of colorectal cancer after adjusting for age, gender and smoking status. For P757L, patients with the Leu/Leu genotype showed a reduced risk of colorectal cancer (adjusted OR = 0.398, 95% CI 0.183-0.866) when the Pro/Leu and Pro/Pro genotypes were combined and used as the reference. The Leu/Leu genotype also had a reduced risk (adjusted OR = 0.373, 95% CI 0.164-0.850) when the Pro/Leu genotype was used as the reference. Individuals who carried both putative risk genotypes (Thr/Met and Met/Met for T439M and Pro/Leu for P757L) showed an adjusted OR of 4.95 (95% CI 1.56-15.7) compared with those who carried both low risk genotypes. Analysis of microsatellite instability (MSI) revealed that tumors from individuals who carried both putative risk genotypes tended to have a higher frequency of MSI positives than those from patients who carried both low risk genotypes, although a significant correlation was not found between EXO1 genotype and MSI status. This is the first report to provide evidence for an association of EXO1 gene polymorphisms with colorectal cancer risk. The EXO1 genotypes were not associated with any clinicopathological characteristics in colorectal cancer patients.