Genetic polymorphisms in C-reactive protein increase cancer susceptibility

Inflammation characterized by release of reactive oxygen/nitrogen species, formation of new blood vessels, degradation of tissues, induction of proliferation and inhibition of apoptosis is a pathophysiologic process involved in oncogenesis via various pathways1. A significant correlation between inflammation and human cancer was first established almost 20 decade years ago2, and inflammatory reactions have received widespread attention in cancer community ever since. Multiple epidemiologic and experimental studies have presented evidence supporting a causative role of chronic inflammation in carcinogenesis of numerous cancers3,4,5. Inflammation is mediated by cytokines and understanding the relevance of pro-inflammatory cytokine pathways to cancer aetiology may gain deeper insights into the molecular mechanisms. C-reactive protein (CRP), known as an inflammatory biomarker, is generated by liver in response to IL-6 which in turn upregulates serum levels of CRP6. Higher levels have been associated with the onset and development of cancer7,8. The CRP gene located at chromosome 1q21–1q23 consists of two exons and spans 1.9 kb in length. To date, there have been 29 single nucleotide polymorphisms (SNPs) identified in the CRP gene (http://www.ncbi.nlm.nih.gov/SNP). A panel of SNPs is shown to regulate CRP levels in the blood9,10,11,12. Therefore, an ideal way to investigate the role of human CRP gene in cancer susceptibility is to estimate the impact of SNPs within the region on the malignant progression. Recently, retrospective and prospective studies in diverse populations have examined the association between cancer susceptibility and CRP SNPs13,14,15, with two non-synonymous polymorphisms (+942G>C, dbSNP ID: rs1800947; 1846C>T, dbSNP ID: rs1205) most extensively studied. However, there is substantial discrepancy in the results most likely due to the relatively small sample size. The goal of this meta-analysis was to comprehensively examine the relationship between the two CRP SNPs and cancer susceptibility.