Studies On Non-coding Mutations Of C-reactive Protein In Tumorigenesis

Inflammation and genome instability underlie the development of cancer. C-reactive protein (CRP) is a classic inflammatory acute phase protein which is used as a non-specific marker of inflammation. There have been many reports on the association of CRP and cancer so far. However, it is still controversial whether CRP is just a marker of inflammation in cancer or CRP plays a direct role in tumorigenesis. It is of great significance on cancer therapy for the latter view. We occasionally find the abnormal genotype of CRP -286 site in cancer cell lines, implying mutation of CRP-286 site in tumorigenesis. We then compared the cancer tissue with the normal tissue from the same patient finding that there is a high prevalence of -286 C>A mutation at the CRP gene promoter. The following work shows that this mutation eliminates the CpG methylation site which upregulates the expression of CRP. After examining there is no similar mutations of other SNPs we have realized that the -286SNP mutation is specific selected in tumorigenesis. Further analysis reveals that mutations of CRP and p53 or K-ras appear to be unrelated, while the-286 SNP mutations of CRP tend to co-occur with mutated APC particularly in colorectal cancer implying an interaction between CRP and Wnt signaling pathway in tumorigenesis.