Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran
Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran
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DOI：
10.1007/s11033-011-1434-6
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发表时间：
2012-05-01
影响因子：
2.8
通讯作者：
Mostafavi-pour, Zohreh
中科院分区：
文献类型：
--
作者：
Naghibalhossaini, Fakhraddin;Zamani, Mozhdeh;Mostafavi-pour, Zohreh
WNT信号在大多数人结直肠癌（CRC）中失调。启动子甲基化已被提出作为肿瘤中抑制基因的替代机制。为了深入了解结直肠癌发生过程中WNT通路的甲基化沉默，我们通过甲基化特异性PCR检测了112例散发性结直肠肿瘤中APC、Axin 1、Axin 2和GSK 3 β 4个基因的异常甲基化谱。已经表明Axin 2 C148 T SNP与发展某些类型癌症的风险相关。为了评估Axin 2 SNP对CRC易感性的贡献，我们通过PCR-RFLP检测了CRC患者和170名健康对照者的Axin 2 C148 T基因型。CRCs中至少有一个基因甲基化的频率为18.75%。Axin 2和APC基因的启动子甲基化分别在7.1%和11.9%的肿瘤中检测到。Gsk 3 β和Axin 1基因在这些肿瘤系列中未发现异常甲基化。APC基因甲基化状态与临床参数无明显相关性。Axin 2基因启动子区甲基化与性别有关，女性发生率更高（P = 0.002）。Axin 2 C148 T基因型在患者和对照组中的频率相似。此外，在按年龄、性别和吸烟状况分层的患者中，我们观察到Axin 2 SNP与CRC风险之间没有关联。然而，与近端患者相比，杂合子CT基因型与远端患者CRC风险降低相关（OR = 0.3; 95%CI 0.1-0.9，P = 0.04）。我们的研究结果表明Axin 1和GSK 3 β甲基化在结直肠癌发生中起次要作用。
The WNT signaling is deregulated in most human colorectal cancers (CRC). Promoter methylation has been proposed as an alternative mechanism to inactivate genes in tumors. To gain insight into the methylation silencing of the WNT pathway during colorectal carcinogenesis, we examined the aberrant methylation profile of four genes, APC, Axin1, Axin2, and GSK3 beta in an unselected series of 112 sporadic colorectal tumors by methylation specific PCR. It has been suggested that the Axin2 C148T SNP is associated with the risk of developing certain types of cancers. To assess the contribution of Axin2 SNP to CRC susceptibility, we examined the Axin2 C148T genotype in CRC patients and 170 healthy controls by PCR-RFLP. The frequency of CRCs with at least one gene methylated was 18.75%. Promoter methylation of Axin2 and APC genes was detected in 7.1 and 11.9% of tumors, respectively. No aberrant methylation was found in Gsk3 beta and Axin1 gene in these tumor series. The methylation status of APC had no significant association with clinical parameters. But, promoter methylation of Axin2 was sex-related, occurring more frequently in females (P = 0.002). The frequency of Axin2 C148T genotypes were similar in patients and controls. Moreover, we observed no association between the Axin2 SNP and risk of CRC in patients stratified by age, sex, and smoking status. However, the heterozygote CT genotype was associated with a reduced CRC risk in distal patients compared with proximal patients (OR = 0.3; 95% CI 0.1-0.9, P = 0.04). Our findings indicate that Axin1 and GSK3 beta methylation play a minor role in colorectal carcinogenesis.