Genetic variation in the promoter of DNMT3B is associated with the risk of colorectal cancer
Genetic variation in the promoter of DNMT3B is associated with the risk of colorectal cancer
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DOI：
10.1007/s00384-011-1199-3
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发表时间：
2011-09-01
影响因子：
2.8
通讯作者：
Wang, Shukui
中科院分区：
文献类型：
--
作者：
Bao, Qian;He, Bangshun;Wang, Shukui
目的DNA甲基转移酶-3B（DNMT 3B）在肿瘤发生过程中异常甲基化的产生中起重要作用。DNMT 3B基因多态性可能影响DNMT 3B酶活性对DNA甲基化的影响，从而调节结直肠癌（CRC）的易感性。（rs 2424913）和-579G>T（rs 1569686）]进行检测结果-579G等位基因与结直肠癌的发病风险显著相关，与结直肠癌患者的发病风险显著相关，与结直肠癌患者的发病风险显著相关，与结直肠癌患者的发病风险显著相关（调整OR，0.50; 95%CI，0.35-0.72; P=0.0002）。然而，DNMT 3B-149 CT基因型与CRC的风险无关（校正OR，0.48; 95%CI，0.18-1.30; P=0.151）。分层分析显示，大肠癌和直肠癌的危险性均以增加为主，原发部位对大肠癌的危险性无影响。结论-579G等位基因是大肠癌发生的潜在保护因素。
Purpose DNA methyltransferase-3B (DNMT3B) plays an important role in the generation of aberrant methylation in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B enzyme activity on DNA methylation, thereby modulating the susceptibility to colorectal cancer (CRC).Methods The polymorphisms in the promoter region of the DNMT3B gene [-149C>T (rs2424913) and -579G>T (rs1569686)] were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and a total of 544 CRC patients and 533 age-and sex-matched healthy controls were enrolled in the case-control study.Results The results showed that the -579G allele was associated with a significantly decreased risk of CRC (adjusted OR, 0.50; 95% CI, 0.35-0.72; P=0.0002) when compared with the -579TT genotype. However, the DNMT3B-149CT genotype was not associated with the risk of CRC (adjusted OR, 0.48; 95% CI, 0.18-1.30; P=0.151). In addition, stratification analysis revealed that the increased risk was predominant in both colon cancer and rectal cancer showing no effect of primary occurrence site.Conclusion Our research demonstrated the -579G allele was a potential protective factor for the occurrence of CRC.