Recurrent mutations at C-reactive protein gene promoter SNP position −286 in human cancers

Genetic alteration and inflammation underlie the development of cancer [1]. C-reactive protein (CRP) is the most widely used nonspecific marker of inflammation [2], whose serum level has been shown to be associated with the risk and prognosis of several types of cancer [3]. Accumulating evidence supports a role of CRP as a pattern recognition receptor in the innate immunity and inflammation [4]; however, its exact function remains to be defined because mouse is not an appropriate animal model for CRP [5]. Moreover, as a prototypical acute phase reactant, the 2-3-order fluctuation in the serum level of CRP has raised the concern that this molecule is not likely a fine modulator of inflammation [2]. These make it difficult to dissect the contribution of CRP in diseases featured by chronic inflammation, including atherosclerosis [2] and cancer [3]. What makes things even more complicated is the fact that large-scale genetic epidemiologic studies do not support a causal association of CRP with these diseases [6, 7]. Therefore, it remains elusive whether CRP is a passive marker or plays a direct role in tumorigenesis.