Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or...

Full description

Saved in:
Bibliographic Details
Published inPloS one Vol. 9; no. 7; p. e102418
Main Authors Su, Hai-Xiang, Zhou, Hai-Hong, Wang, Ming-Yu, Cheng, Jin, Zhang, Shi-Chao, Hui, Feng, Chen, Xue-Zhong, Liu, Shan-Hui, Liu, Qin-Jiang, Zhu, Zi-Jiang, Hu, Qing-Rong, Wu, Yi, Ji, Shang-Rong
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 15.07.2014
Public Library of Science (PLoS)
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: SRJ YW HXS. Performed the experiments: HXS HHZ MYW JC SCZ FH SHL. Analyzed the data: SRJ YW HXS MYW. Contributed reagents/materials/analysis tools: XZC QJL ZJZ QRH. Wrote the paper: SRJ YW HXS.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0102418