Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran
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- 作者：Fakhraddin Naghibalhossaini (12) fakhraddin.naghibalhossaini@mail.mcgill.ca
Mozhdeh Zamani (1)
Pooneh Mokarram (1)
Islam Khalili (1)
Mozhgan Rasti (1)
Zohreh Mostafavi-pour (13) - 关键词：Colon cancer – ; WNT signaling – ; AXIN2 P50S SNP – ; Methylation
- 刊名：Molecular Biology Reports
- 出版年：2012
- 出版时间：May 2012
- 年：2012
- 卷：39
- 期：5
- 页码：6171-6178
- 全文大小：285.1 KB
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- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Animal Anatomy, Morphology and Histology
Animal Biochemistry - 出版者：Springer Netherlands
- ISSN：1573-4978
文摘
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 GSK3β 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 Gsk3β 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 GSK3β methylation play a minor role in colorectal carcinogenesis.