title: Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk.
abstract: 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.
authors.affiliation: Gansu Provincial Academic Institute for Medical Research, Lanzhou, P.R. China; The Gansu Provincial Tumor Hospital, Lanzhou, P.R. China.
authors.forename: Hai-Xiang
authors.initials: HX
authors.lastname: Su
authors.affiliation: Gansu Provincial Academic Institute for Medical Research, Lanzhou, P.R. China; The Gansu Provincial Tumor Hospital, Lanzhou, P.R. China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Shi-Chao
authors.initials: SC
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Hui
authors.affiliation: Gansu Provincial Academic Institute for Medical Research, Lanzhou, P.R. China; The Gansu Provincial Tumor Hospital, Lanzhou, P.R. China.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Shan-Hui
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Gansu Provincial Academic Institute for Medical Research, Lanzhou, P.R. China; The Gansu Provincial Tumor Hospital, Lanzhou, P.R. China.
authors.forename: Qin-Jiang
authors.initials: QJ
authors.lastname: Liu
authors.affiliation: Gansu Provincial Academic Institute for Medical Research, Lanzhou, P.R. China; The Gansu Provincial Tumor Hospital, Lanzhou, P.R. China.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Zhu
authors.affiliation: Gansu Provincial Academic Institute for Medical Research, Lanzhou, P.R. China; The Gansu Provincial Tumor Hospital, Lanzhou, P.R. China.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, P.R. China.
authors.forename: Shang-Rong
authors.initials: SR
authors.lastname: Ji
mesh_terms: D002097:C-Reactive Protein / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: D051153:Wnt Proteins; D002097:C-Reactive Protein